Dlx5 regulates regional development of the branchial arches and sensory capsules

Development ◽  
1999 ◽  
Vol 126 (17) ◽  
pp. 3831-3846 ◽  
Author(s):  
M.J. Depew ◽  
J.K. Liu ◽  
J.E. Long ◽  
R. Presley ◽  
J.J. Meneses ◽  
...  
Keyword(s):  
Homeobox Gene ◽  
Semicircular Canals ◽  
Otic Vesicle ◽  
Craniofacial Malformations ◽  
General Role ◽  
Targeted Deletion ◽  
Mandibular Arch ◽  
Branchial Arches ◽  
Otic Placode ◽  
The Right

We report the generation and analysis of mice homozygous for a targeted deletion of the Dlx5 homeobox gene. Dlx5 mutant mice have multiple defects in craniofacial structures, including their ears, noses, mandibles and calvaria, and die shortly after birth. A subset (28%) exhibit exencephaly. Ectodermal expression of Dlx5 is required for the development of olfactory and otic placode-derived epithelia and surrounding capsules. The nasal capsules are hypoplastic (e.g. lacking turbinates) and, in most cases, the right side is more severely affected than the left. Dorsal otic vesicle derivatives (e. g. semicircular canals and endolymphatic duct) and the surrounding capsule, are more severely affected than ventral (cochlear) structures. Dlx5 is also required in mandibular arch ectomesenchyme, as the proximal mandibular arch skeleton is dysmorphic. Dlx5 may control craniofacial development in part through the regulation of the goosecoid homeobox gene. goosecoid expression is greatly reduced in Dlx5 mutants, and both goosecoid and Dlx5 mutants share a number of similar craniofacial malformations. Dlx5 may perform a general role in skeletal differentiation, as exemplified by hypomineralization within the calvaria. The distinct focal defects within the branchial arches of the Dlx1, Dlx2 and Dlx5 mutants, along with the nested expression of their RNAs, support a model in which these genes have both redundant and unique functions in the regulation of regional patterning of the craniofacial ectomesenchyme.

Nkx5-1 controls semicircular canal formation in the mouse inner ear

Development ◽  
1998 ◽  
Vol 125 (1) ◽  
pp. 33-39 ◽  
Author(s):  
T. Hadrys ◽  
T. Braun ◽  
S. Rinkwitz-Brandt ◽  
H.H. Arnold ◽  
E. Bober
Keyword(s):  
Homologous Recombination ◽  
Inner Ear ◽  
Homeobox Gene ◽  
Semicircular Canals ◽  
Otic Vesicle ◽  
Null Mutation ◽  
Complex Structures ◽  
Vestibular Organ ◽  
Inner Ear Development ◽  
Vestibular Organs

The inner ear develops from the otic vesicle, a one-cell-thick epithelium, which eventually transforms into highly complex structures including the sensory organs for balance (vestibulum) and hearing (cochlea). Several mouse inner ear mutations with hearing and balance defects have been described but for most the underlying genes have not been identified, for example, the genes controlling the development of the vestibular organs. Here, we report the inactivation of the homeobox gene, Nkx5-1, by homologous recombination in mice. This gene is expressed in vestibular structures throughout inner ear development. Mice carrying the Nkx5-1 null mutation exhibit behavioural abnormalities that resemble the typical hyperactivity and circling movements of the shaker/waltzer type mutants. The balance defect correlates with severe malformations of the vestibular organ in Nkx5-1(−/−) mutants, which fail to develop the semicircular canals. Nkx5-1 is the first ear-specific molecule identified to play a crucial role in the formation of the mammalian vestibular system.

scholarly journals Mutations affecting development of the zebrafish ear

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 275-283 ◽  
Author(s):  
J. Malicki ◽  
A.F. Schier ◽  
L. Solnica-Krezel ◽  
D.L. Stemple ◽  
S.C. Neuhauss ◽  
...  
Keyword(s):  
Large Scale ◽  
Semicircular Canals ◽  
Brain Morphology ◽  
Otic Vesicle ◽  
Ear Morphology ◽  
Entry Points ◽  
Otic Placode ◽  
Phenotypic And Genetic Characterization ◽  
Zebrafish Embryogenesis

In a large scale screen for genetic defects in zebrafish embryogenesis we identified mutations affecting several aspects of ear development, including: specification of the otic placode, growth of the otic vesicle (otocyst), otolith formation, morphogenesis of the semicircular canals and differentiation of the otic capsule. Here we report initial phenotypic and genetic characterization of 20 of these mutations defining 13 independent loci. Embryos mutant at the quadro locus display abnormal specification of the otic placode. As revealed by dlx-3 expression, the otic field in the mutant embryos is smaller or split into two fields. At later stages of development the ear of quadro mutants is frequently divided into two smaller, incomplete units. Four loci affect ear shape shortly after formation of the otic vesicle. All of them also display abnormal brain morphology. Mutations in five loci result in the absence of otolith formation; two of these also produce changes of ear morphology. Two loci, little richard and golas, affect morphology of the otic vesicle shortly before formation of the semicircular canals. In both cases the morphogenesis of the semicircular canals is disrupted. Finally, the antytalent locus is involved in late expansion of the ear structure. Analysis of mutations presented here will strengthen our understanding of vertebrate ear morphogenesis and provide novel entry points to its genetic analysis.

scholarly journals Two regulatory genes, cNkx5-1 and cPax2, show different responses to local signals during otic placode and vesicle formation in the chick embryo

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 645-654 ◽  
Author(s):  
H. Herbrand ◽  
S. Guthrie ◽  
T. Hadrys ◽  
S. Hoffmann ◽  
H.H. Arnold ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Homeobox Gene ◽  
Lateral Wall ◽  
Otic Vesicle ◽  
Ear Development ◽  
Inner Ear Development ◽  
Dynamic Expression ◽  
Otic Placode ◽  
Transplantation Experiments ◽  
Correct Expression

The early stages of otic placode development depend on signals from neighbouring tissues including the hindbrain. The identity of these signals and of the responding placodal genes, however, is not known. We have identified a chick homeobox gene cNkx5-1, which is expressed in the otic placode beginning at stage 10 and exhibits a dynamic expression pattern during formation and further differentiation of the otic vesicle. In a series of heterotopic transplantation experiments, we demonstrate that cNkx5-1 can be activated in ectopic positions. However, significant differences in otic development and cNkx5-1 gene activity were observed when placodes were transplanted into the more rostral positions within the head mesenchyme or into the wing buds of older hosts. These results indicate that only the rostral tissues were able to induce and/or maintain ear development. Ectopically induced cNkx5-1 expression always reproduced the endogenous pattern within the lateral wall of the otocyst that is destined to form vestibular structures. In contrast, cPax2 which is expressed in the medial wall of the early otic vesicle later forming the cochlea never resumed its correct expression pattern after transplantation. Our experiments illustrate that only some aspects of gene expression and presumably pattern formation during inner ear development can be established and maintained ectopically. In particular, the dorsal vestibular structures seem to be programmed earlier and differently from the ventral cochlear part.

Interstitial Nucleus of Cajal Encodes Three-Dimensional Head Orientations in Fick-Like Coordinates

2007 ◽  
Vol 97 (1) ◽  
pp. 604-617 ◽  
Author(s):  
Eliana M. Klier ◽  
Hongying Wang ◽  
J. Douglas Crawford
Keyword(s):  
Coordinate System ◽  
Degrees Of Freedom ◽  
Three Dimensional ◽  
Semicircular Canals ◽  
Head Rotation ◽  
Head Orientation ◽  
Interstitial Nucleus Of Cajal ◽  
The Gaze ◽  
Behavioral Constraints ◽  
The Right

Two central, related questions in motor control are 1) how the brain represents movement directions of various effectors like the eyes and head and 2) how it constrains their redundant degrees of freedom. The interstitial nucleus of Cajal (INC) integrates velocity commands from the gaze control system into position signals for three-dimensional eye and head posture. It has been shown that the right INC encodes clockwise (CW)-up and CW-down eye and head components, whereas the left INC encodes counterclockwise (CCW)-up and CCW-down components, similar to the sensitivity directions of the vertical semicircular canals. For the eyes, these canal-like coordinates align with Listing’s plane (a behavioral strategy limiting torsion about the gaze axis). By analogy, we predicted that the INC also encodes head orientation in canal-like coordinates, but instead, aligned with the coordinate axes for the Fick strategy (which constrains head torsion). Unilateral stimulation (50 μA, 300 Hz, 200 ms) evoked CW head rotations from the right INC and CCW rotations from the left INC, with variable vertical components. The observed axes of head rotation were consistent with a canal-like coordinate system. Moreover, as predicted, these axes remained fixed in the head, rotating with initial head orientation like the horizontal and torsional axes of a Fick coordinate system. This suggests that the head is ordinarily constrained to zero torsion in Fick coordinates by equally activating CW/CCW populations of neurons in the right/left INC. These data support a simple mechanism for controlling head orientation through the alignment of brain stem neural coordinates with natural behavioral constraints.

scholarly journals Persistent Upbeat Positional Nystagmus in a Patient with Bilateral Posterior Canal Benign Paroxysmal Positional Vertigo

2019 ◽  
Vol 2019 ◽  
pp. 1-3
Author(s):  
Akihide Ichimura ◽  
Shigeto Itani
Keyword(s):  
Supine Position ◽  
Benign Paroxysmal Positional Vertigo ◽  
Semicircular Canals ◽  
Downbeat Nystagmus ◽  
Positional Vertigo ◽  
Head Roll ◽  
The Right ◽  
Upbeat Nystagmus ◽  
Torsional Nystagmus ◽  
Paroxysmal Positional Vertigo

Here, we report a patient with persistent positional upbeat nystagmus in a straight supine position with no evident abnormal central nervous system findings. A 43-year-old woman with rotatory positional vertigo and nausea visited our clinic 7 days after the onset. Initially, we observed persistent upbeat nystagmus in straight supine position with a latency of 2 s during the supine head roll test. However, an upbeat nystagmus disappeared on turning from straight to the left ear-down supine position, and while turning from the left to right ear-down position, an induced slight torsional nystagmus towards the right for >22 s was observed. In the Dix–Hallpike test, the left head-hanging position provoked torsional nystagmus towards the right for 50 s. In prone seated position, downbeat nystagmus with torsional component towards the left was observed for 45 s. Neurological examination and brain computed tomography revealed no abnormal findings. We speculated that persistent positional upbeat nystagmus in this patient was the result of canalolithiasis of benign paroxysmal positional vertigo of bilateral posterior semicircular canals.

scholarly journals THE CLINICAL CASE OF HEMIFACIAL MICROSOMIA IN THE NEWBORN BOY FROM MOTHER WITH Z-21

2021 ◽  
Vol 11 (2(40)) ◽  
pp. 64-67
Author(s):  
I.V. Lastivka ◽  
A.G. Babintseva ◽  
V.V. Antsupova ◽  
А.І. Peryzhniak ◽  
І.V. Koshurba ◽  
...  
Keyword(s):  
Clinical Case ◽  
Septal Defect ◽  
Neonatal Period ◽  
Hemifacial Microsomia ◽  
Internal Factors ◽  
Vascular Abnormalities ◽  
Branchial Arches ◽  
The Face ◽  
The Right

Hemifacial Microsomia (HFM) is a term used to identify facial deformities associated with the development ofthe first and second pairs of branchial arches, characterized by underdevelopment of one half of the face. One typeof hemifacial microsomia is oculo-auriculo-vertebral dysplasia or Goldenhar syndrome.The incidence of HFM is 1:3500-1:7000 of live births and occurs in 1 case per 1000 children with congenitaldeafness. The ratio of boys to girls is 3:2. The etiology and type of inheritance is studied insufficiently. There are threepossible pathogenetic models: vascular abnormalities and hemorrhages in the craniofacial region, damage of Meckel'scartilage, and abnormal cell development of the cranial nerve crest. Environmental factors, maternal internal factors,and genetic factors (OTX2, PLCD3, and MYT1 mutations) may also cause the development of hemifacial microsomia.The article demonstrates a clinical case of hemifacial microsomia in a newborn boy from a mother with Z-21 inthe form of deformation of the left auricle with atresia of the auditory canal and "false" ears on the right, combinedwith congenital anomaly of heart (atrial septal defect) and brain (hypoplasia of the corpus callosum).Emphasis is placed on the need of involving a multidisciplinary team of specialists in the management of thispatient both in the neonatal period and in the system of subsequent follow-up.

Defining Subphenotypes for Tooth Agenesis: Does Side Matter?

2009 ◽  
Vol 34 (2) ◽  
pp. 169-172 ◽  
Author(s):  
Marcelo de Castro Costa ◽  
Erika Calvano Küchler ◽  
Paulo Ferreira Garcia Filho ◽  
Adriana Modesto ◽  
Alexandre Rezende Vieira
Keyword(s):  
Genetic Factors ◽  
Large Cohort ◽  
Differentially Expressed ◽  
Tooth Agenesis ◽  
Panoramic Radiographs ◽  
Mandibular Arch ◽  
Specific Hypothesis ◽  
Study Population ◽  
The Right

Objectives: The etiology of tooth agenesis is still poorly understood. The identification of sub-populations with specific types of hypodontia (subphenotypes) would allow testing the specific hypothesis that certain genetic factors contribute to the specific subphenotype. The aim of this work was assessing a large cohort to verify if preferential tooth agenesis subphenotypes could be identified. Method: Panoramic radiographs of 1052 cases were examined and 1034 were used in this study. The presence of tooth agenesis was assessed in the study population. Results: The frequency of tooth agenesis in the studied population was 3.77%. While bilateral cases did not differ in the frequency of agenesis by arch (p = 0.8), unilateral cases presented more commonly agenesis on the mandibular arch (p = 0.03). This result was clearly driven by the frequency of second premolar agenesis, which was the most common absent tooth in the studied population. Unilateral lower second premolar agenesis was found more often than bilateral agenesis (p = 0.047). Conclusions:Our findings that unilateral lower second premolar agenesis is more common than bilateral agenesis, with a trend for unilateral agenesis being more common on the right side may suggest specific genetic factors may be differentially expressed depending on the side.

Effect of temperature differentials upon reconstitution of embryonic primordia in Ambystoma

Development ◽  
1971 ◽  
Vol 25 (3) ◽  
pp. 339-345
Author(s):  
Jean Piatt
Keyword(s):  
Statistical Analysis ◽  
Ambystoma Maculatum ◽  
Effect Of Temperature ◽  
Otic Vesicle ◽  
Regenerative Capacity ◽  
Rate Of Development ◽  
The Difference ◽  
The Right ◽  
Two Temperature

Eggs of Ambystoma maculatum in early stages of development were separated into two groups and maintained at 5 and 14 °C, respectively. In one series of animals comprising both temperature groups, the right otic vesicle was extirpated at stage 27. In another series the right forelimb disc was extirpated at stage 30. Following operation, animals of both groups were kept at 18 °C. Frequency and extent of reconstitution were compared between the two temperature groups. The 5° group was superior to the 14° group in the number of ears and forelimbs reconstituted. The extent of ear reconstitution and the initial quality of forelimb reconstitution were also superior in the 5° group. Statistical analysis of the data indicates that the difference between the two temperature groups is highly significant in both series. It is concluded that a slower pre-operative rate of development, caused by hypothermia, enhances the regenerative capacity of both ear and forelimb fields in the salamander embryo.

Developmental expression of transforming growth factors alpha and beta in mouse fetus

1988 ◽  
Vol 8 (8) ◽  
pp. 3415-3422
Author(s):  
J N Wilcox ◽  
R Derynck
Keyword(s):  
Transforming Growth Factor ◽  
Developmental Expression ◽  
Otic Vesicle ◽  
Tgf Beta ◽  
Hematopoietic Organ ◽  
Mouse Fetus ◽  
Branchial Arches ◽  
Factor Alpha ◽  
And Function

Expression of mRNA for transforming growth factor alpha (TGF-alpha) and TGF-beta 1 during the fetal development of mice was evaluated by in situ hybridization. TGF-alpha mRNA was detected in 9- and 10-day fetuses but was absent in older fetuses. TGF-alpha mRNA-containing cells were found in the placenta, otic vesicle, oral cavity, pharyngeal pouch, first and second branchial arches, and developing kidneys. mRNA for TGF-beta 1 was present in hematopoietic cells of blood islands and capillaries and in the liver as it began to bud off on day 10 and function as a hematopoietic organ.

Mutations affecting development of the zebrafish inner ear and lateral line

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 241-254 ◽  
Author(s):  
T.T. Whitfield ◽  
M. Granato ◽  
F.J. van Eeden ◽  
U. Schach ◽  
M. Brand ◽  
...  
Keyword(s):  
Inner Ear ◽  
Lateral Line ◽  
Large Scale ◽  
Sensory System ◽  
Semicircular Canals ◽  
Abnormal Development ◽  
Pigment Cells ◽  
Otic Vesicle ◽  
In The Wild ◽  
Complementation Groups

Mutations giving rise to anatomical defects in the inner ear have been isolated in a large scale screen for mutations causing visible abnormalities in the zebrafish embryo (Haffter, P., Granato, M., Brand, M. et al. (1996) Development 123, 1–36). 58 mutants have been classified as having a primary ear phenotype; these fall into several phenotypic classes, affecting presence or size of the otoliths, size and shape of the otic vesicle and formation of the semicircular canals, and define at least 20 complementation groups. Mutations in seven genes cause loss of one or both otoliths, but do not appear to affect development of other structures within the ear. Mutations in seven genes affect morphology and patterning of the inner ear epithelium, including formation of the semicircular canals and, in some, development of sensory patches (maculae and cristae). Within this class, dog-eared mutants show abnormal development of semicircular canals and lack cristae within the ear, while in van gogh, semicircular canals fail to form altogether, resulting in a tiny otic vesicle containing a single sensory patch. Both these mutants show defects in the expression of homeobox genes within the otic vesicle. In a further class of mutants, ear size is affected while patterning appears to be relatively normal; mutations in three genes cause expansion of the otic vesicle, while in little ears and microtic, the ear is abnormally small, but still contains all five sensory patches, as in the wild type. Many of the ear and otolith mutants show an expected behavioural phenotype: embryos fail to balance correctly, and may swim on their sides, upside down, or in circles. Several mutants with similar balance defects have also been isolated that have no obvious structural ear defect, but that may include mutants with vestibular dysfunction of the inner ear (Granato, M., van Eeden, F. J. M., Schach, U. et al. (1996) Development, 123, 399–413,). Mutations in 19 genes causing primary defects in other structures also show an ear defect. In particular, ear phenotypes are often found in conjunction with defects of neural crest derivatives (pigment cells and/or cartilaginous elements of the jaw). At least one mutant, dog-eared, shows defects in both the ear and another placodally derived sensory system, the lateral line, while hypersensitive mutants have additional trunk lateral line organs.

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