scholarly journals Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage

2020 ◽  
Vol 8 (4) ◽  
pp. 31
Author(s):  
Ines Desanlis ◽  
Rachel Paul ◽  
Marie Kmita
Keyword(s):  
Global Change ◽  
Hox Genes ◽  
Limb Bud ◽  
Temporal Expression ◽  
Distal Limb ◽  
Limb Patterning ◽  
Previous Evidence ◽  
Limb Mesenchyme ◽  
Mouse Limb ◽  
Anterior Posterior

Limb patterning relies in large part on the function of the Hox family of developmental genes. While the differential expression of Hox genes shifts from the anterior–posterior (A–P) to the proximal–distal (P–D) axis around embryonic day 11 (E11), whether this shift coincides with a more global change of A–P to P–D patterning program remains unclear. By performing and analyzing the transcriptome of the developing limb bud from E10.5 to E12.5, at single-cell resolution, we have uncovered transcriptional trajectories that revealed a general switch from A–P to P–D genetic program between E10.5 and E11.5. Interestingly, all the transcriptional trajectories at E10.5 end with cells expressing either proximal or distal markers suggesting a progressive acquisition of P–D identity. Moreover, we identified three categories of genes expressed in the distal limb mesenchyme characterized by distinct temporal expression dynamics. Among these are Hoxa13 and Hoxd13 (Hox13 hereafter), which start to be expressed around E10.5, and importantly the binding of the HOX13 factors was observed within or in the neighborhood of several of the distal limb genes. Our data are consistent with previous evidence suggesting that the transition from the early/proximal to the late/distal transcriptome of the limb mesenchyme largely relies on HOX13 function. Based on these results and the evidence that HOX13 factors restrict Hoxa11 expression to the proximal limb, in progenitor cells of the zeugopod, we propose that HOX13 act as a key determinant of P–D patterning.

Why we have (only) five fingers per hand: hox genes and the evolution of paired limbs

Development ◽  
1992 ◽  
Vol 116 (2) ◽  
pp. 289-296 ◽  
Author(s):  
C.J. Tabin
Keyword(s):  
Limb Development ◽  
Hox Genes ◽  
Expression Patterns ◽  
Limb Bud ◽  
Developmental Constraint ◽  
Limb Morphogenesis ◽  
Different Types ◽  
Embryonic Limb ◽  
Limb Pattern ◽  
Anterior Posterior

Limb development has long been a model system for studying vertebrate pattern formation. The advent of molecular biology has allowed the identification of some of the key genes that regulate limb morphogenesis. One important class of such genes are the homeobox-containing, or Hox genes. Understanding of the roles these genes play in development additionally provides insights into the evolution of limb pattern. Hox gene expression patterns divide the embryonic limb bud into five sectors along the anterior/posterior axis. The expression of specific Hox genes in each domain specifies the developmental fate of that region. Because there are only five distinct Hox-encoded domains across the limb bud there is a developmental constraint prohibiting the evolution of more than five different types of digits. The expression patterns of Hox genes in modern embryonic limb buds also gives clues to the shape of the ancestral fin field from which the limb evolved, hence elucidating the evolution of the tetrapod limb.

Cell adhesion and chondrogenesis in brachypod mouse limb mesenchyme: fragment fusion studies

Development ◽  
1978 ◽  
Vol 48 (1) ◽  
pp. 161-168
Author(s):  
Jackie Duke ◽  
William A. Elmer
Keyword(s):  
Cell Adhesion ◽  
Limb Development ◽  
Cell Interactions ◽  
Limb Bud ◽  
Limb Mesenchyme ◽  
Mouse Mutation ◽  
Mouse Limb

This study is a continuing investigation of the effect of the brachypod mouse mutation on cell interactions and chondrogenesis during early limb development. In this report, cell adhesiveness was assessed in fused fragments of brachypod and normal limb-bud mesenchyme. Examination of the interface of fused distal postaxial limb fragments show brachypod limb mesenchyme to be more adhesive than normal limb mesenchyme. Chondrogenesis within brachypod fragments is delayed and less extensive than in normal fragments. In addition, chondrogenesis within normal fragments is not affected by the juxtaposition of thebrachypod fragment, and vice versa.

Distinct signaling molecules control Hoxa-11 and Hoxa-13 expression in the muscle precursor and mesenchyme of the chick limb bud

Development ◽  
1999 ◽  
Vol 126 (12) ◽  
pp. 2771-2783 ◽  
Author(s):  
K. Hashimoto ◽  
Y. Yokouchi ◽  
M. Yamamoto ◽  
A. Kuroiwa
Keyword(s):  
Growth Factor ◽  
Muscle Development ◽  
Hox Genes ◽  
Expression Patterns ◽  
Precursor Cells ◽  
Limb Bud ◽  
Posterior Region ◽  
Limb Muscle ◽  
Limb Mesenchyme ◽  
Myogenic Precursor

The limb muscles, originating from the ventrolateral portion of the somites, exhibit position-specific morphological development through successive splitting and growth/differentiation of the muscle masses in a region-specific manner by interacting with the limb mesenchyme and the cartilage elements. The molecular mechanisms that provide positional cues to the muscle precursors are still unknown. We have shown that the expression patterns of Hoxa-11 and Hoxa-13 are correlated with muscle patterning of the limb bud (Yamamoto et al., 1998) and demonstrated that muscular Hox genes are activated by signals from the limb mesenchyme. We dissected the regulatory mechanisms directing the unique expression patterns of Hoxa-11 and Hoxa-13 during limb muscle development. HOXA-11 protein was detected in both the myogenic cells and the zeugopodal mesenchymal cells of the limb bud. The earlier expression of HOXA-11 in both the myogenic precursor cells and the mesenchyme was dependent on the apical ectodermal ridge (AER), but later expression was independent of the AER. HOXA-11 expression in both myogenic precursor cells and mesenchyme was induced by fibroblast growth factor (FGF) signal, whereas hepatocyte growth factor/scatter factor (HGF/SF) maintained HOXA-11 expression in the myogenic precursor cells, but not in the mesenchyme. The distribution of HOXA-13 protein expression in the muscle masses was restricted to the posterior region. We found that HOXA-13 expression in the autopodal mesenchyme was dependent on the AER but not on the polarizing region, whereas expression of HOXA-13 in the posterior muscle masses was dependent on the polarizing region but not on the AER. Administration of BMP-2 at the anterior margin of the limb bud induced ectopic HOXA-13 expression in the anterior region of the muscle masses followed by ectopic muscle formation close to the source of exogenous BMP-2. In addition, NOGGIN/CHORDIN, antagonists of BMP-2 and BMP-4, downregulated the expression of HOXA-13 in the posterior region of the muscle masses and inhibited posterior muscle development. These results suggested that HOXA-13 expression in the posterior muscle masses is activated by the posteriorizing signal from the posterior mesenchyme via BMP-2. On the contrary, the expression of HOXA-13 in the autopodal mesenchyme was affected by neither BMP-2 nor NOGGIN/CHORDIN. Thus, mesenchymal HOXA-13 expression was independent of BMP-2 from polarizing region, but was under the control of as yet unidentified signals from the AER. These results showed that expression of Hox genes is regulated differently in the limb muscle precursor and mesenchymal cells.

Hox genes and growth: early and late roles in limb bud morphogenesis

Development ◽  
1994 ◽  
Vol 1994 (Supplement) ◽  
pp. 181-186
Author(s):  
Bruce A. Morgan ◽  
Cliff Tabin
Keyword(s):  
Limb Development ◽  
Hox Genes ◽  
Limb Bud ◽  
Limb Mesenchyme ◽  
Positional Identity ◽  
Limb Morphogenesis ◽  
Combined Action ◽  
Level Of Understanding ◽  
Hox Clusters ◽  
Hoxd Gene

In recent years, molecular analysis has led to the identification of some of the key genes that control the morphogenesis of the developing embryo. Detailed functional analysis of these genes is rapidly leading to a new level of understanding of how embryonic form is regulated. Understanding the roles that these genes play in development can additionally provide insights into the evolution of morphology. The 5′ genes of the vertebrate Hox clusters are expressed in complex patterns during limb morphogenesis. Various models suggest that the Hoxd genes specify positional identity along the anteroposterior (A-P) axis of the limb. Close examination of the pattern of Hoxd gene expression in the limb suggests that a distinct combination of Hoxd gene expressed in different digit primordia is unlikely to specify each digit independently. The effects of altering the pattern of expression of the Hoxd-11 gene at different times during limb development indicate that the Hoxd genes have separable early and late roles in limb morphogenesis. In their early role, the Hoxd genes are involved in regulating the growth of the undifferentiated limb mesenchyme. Restriction of the expression of successive 5′ Hoxd genes to progressively more posterior regions of the bud results in the asymmetric outgrowth of the limb mesenchyme. Later in limb development, Hoxd genes also regulate the maturation of the nascent skeletal elements. The degree of overlap in function between different Hoxd genes may be different in these early and late roles. The combined action of many Hox genes on distinct developmental processes contribute to pattern asymmetry along the A-P axis.

scholarly journals Fibroblast growth factors (FGFs) prime the limb specific Shh enhancer for chromatin changes that balance histone acetylation mediated by E26 transformation-specific (ETS) factors

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Silvia Peluso ◽  
Adam Douglas ◽  
Alison Hill ◽  
Carlo De Angelis ◽  
Benjamin L Moore ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Limb Bud ◽  
Fibroblast Growth ◽  
Distal Limb ◽  
Inactive State ◽  
Dynamic Events ◽  
Active Enhancer ◽  
Mouse Limb ◽  
Fgf Signalling ◽  
Zone Of Polarizing Activity

Sonic hedgehog (Shh) expression in the limb bud organizing centre called the zone of polarizing activity is regulated by the ZRS enhancer. Here, we examine in mouse and in a mouse limb-derived cell line the dynamic events that activate and restrict the spatial activity of the ZRS. Fibroblast growth factor (FGF) signalling in the distal limb primes the ZRS at early embryonic stages maintaining a poised, but inactive state broadly across the distal limb mesenchyme. The E26 transformation-specific transcription factor, ETV4, which is induced by FGF signalling and acts as a repressor of ZRS activity, interacts with the histone deacetylase HDAC2 and ensures that the poised ZRS remains transcriptionally inactive. Conversely, GABPα, an activator of the ZRS, recruits p300, which is associated with histone acetylation (H3K27ac) indicative of an active enhancer. Hence, the primed but inactive state of the ZRS is induced by FGF signalling and in combination with balanced histone modification events establishes the restricted, active enhancer responsible for patterning the limb bud during development.

scholarly journals Hox genes are essential for the development of eyespots in Bicyclus anynana butterflies

Genetics ◽  
2020 ◽  
Vol 217 (1) ◽  
Author(s):  
Yuji Matsuoka ◽  
Antónia Monteiro
Keyword(s):  
Hox Genes ◽  
Bicyclus Anynana ◽  
Hox Gene ◽  
Novel Traits ◽  
Anterior Posterior ◽  
Anterior Posterior Axis

Abstract The eyespot patterns found on the wings of nymphalid butterflies are novel traits that originated first in hindwings and subsequently in forewings, suggesting that eyespot development might be dependent on Hox genes. Hindwings differ from forewings in the expression of Ultrabithorax (Ubx), but the function of this Hox gene in eyespot development as well as that of another Hox gene Antennapedia (Antp), expressed specifically in eyespots centers on both wings, are still unclear. We used CRISPR-Cas9 to target both genes in Bicyclus anynana butterflies. We show that Antp is essential for eyespot development on the forewings and for the differentiation of white centers and larger eyespots on hindwings, whereas Ubx is essential not only for the development of at least some hindwing eyespots but also for repressing the size of other eyespots. Additionally, Antp is essential for the development of silver scales in male wings. In summary, Antp and Ubx, in addition to their conserved roles in modifying serially homologous segments along the anterior–posterior axis of insects, have acquired a novel role in promoting the development of a new set of serial homologs, the eyespot patterns, in both forewings (Antp) and hindwings (Antp and Ubx) of B. anynana butterflies. We propose that the peculiar pattern of eyespot origins on hindwings first, followed by forewings, could be due to an initial co-option of Ubx into eyespot development followed by a later, partially redundant, co-option of Antp into the same network.

Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and rescues hypodactyly mice

2007 ◽  
Vol 26 (4) ◽  
pp. 224-233 ◽  
Author(s):  
Haruhiko Akiyama ◽  
H. Scott Stadler ◽  
James F. Martin ◽  
Takahiro M. Ishii ◽  
Philip A. Beachy ◽  
...  
Keyword(s):  
Limb Bud ◽  
Mouse Limb
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