Math3 and NeuroD regulate amacrine cell fate specification in the retina

Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 831-842 ◽  
Author(s):  
Tomoyuki Inoue ◽  
Masato Hojo ◽  
Yasumasa Bessho ◽  
Yasuo Tano ◽  
Jacqueline E. Lee ◽  
...  
Keyword(s):  
Cell Fate ◽  
Double Mutant ◽  
Amacrine Cell ◽  
Homeobox Gene ◽  
Amacrine Cells ◽  
Cell Fates ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Normal Number ◽  
Cell Genesis

The basic helix-loop-helix genes Math3 and NeuroD are expressed by differentiating amacrine cells, retinal interneurons. Previous studies have demonstrated that a normal number of amacrine cells is generated in mice lacking either Math3 or NeuroD. We have found that, in Math3-NeuroD double-mutant retina, amacrine cells are completely missing, while ganglion and Müller glial cells are increased in number. In the double-mutant retina, the cells that would normally differentiate into amacrine cells did not die but adopted the ganglion and glial cell fates. Misexpression studies using the developing retinal explant cultures showed that, although Math3 and NeuroD alone only promoted rod genesis, they significantly increased the population of amacrine cells when the homeobox gene Pax6 or Six3 was co-expressed. These results indicate that Math3 and NeuroD are essential, but not sufficient, for amacrine cell genesis, and that co-expression of the basic helix-loop-helix and homeobox genes is required for specification of the correct neuronal subtype.

Extrinsic and intrinsic factors control the genesis of amacrine and cone cells in the rat retina

Development ◽  
1999 ◽  
Vol 126 (3) ◽  
pp. 555-566 ◽  
Author(s):  
M.J. Belliveau ◽  
C.L. Cepko
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Amacrine Cell ◽  
Amacrine Cells ◽  
Environment Change ◽  
Rat Retina ◽  
Cell Fate Decisions ◽  
Cone Cells ◽  
Postnatal Environment

The seven major classes of cells of the vertebrate neural retina are generated from a pool of multipotent progenitor cells. Recent studies suggest a model of retinal development in which both the progenitor cells and the environment change over time (Cepko, C. L., Austin, C. P., Yang, X., Alexiades, M. and Ezzeddine, D. (1996). Proc. Natl. Acad. Sci. USA 93, 589–595). We have utilized a reaggregate culture system to test this model. A labeled population of progenitors from the embryonic rat retina were cultured with an excess of postnatal retinal cells and then assayed for their cell fate choices. We found that the postnatal environment had at least two signals that affected the embryonic cells' choice of fate; one signal inhibited the production of amacrine cells and a second affected the production of cone cells. No increase in cell types generated postnatally was observed. The source of the inhibitor of the amacrine cell fate appeared to be previously generated amacrine cells, suggesting that amacrine cell number is controlled by feedback inhibition. The progenitor cell lost its ability to be inhibited for production of an amacrine cell as it entered M phase of the cell cycle. We suggest that postmitotic cells influence progenitor cell fate decisions, but that they do so in a manner restricted by the intrinsic biases of progenitor cells.

Sectors expressing the homeobox gene liguleless3 implicate a time-dependent mechanism for cell fate acquisition along the proximal-distal axis of the maize leaf

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5097-5106 ◽  
Author(s):  
G.J. Muehlbauer ◽  
J.E. Fowler ◽  
M. Freeling
Keyword(s):  
Cell Fate ◽  
Homeobox Gene ◽  
Longitudinal Axis ◽  
Cell Types ◽  
Transverse Dimension ◽  
Leaf Sheath ◽  
Wild Type ◽  
Cell Fates ◽  
Maize Leaf ◽  
Gradual Process

The longitudinal axis of the maize leaf is composed of, in proximal to distal order, sheath, ligule, auricle and blade. The semidominant Liguleless3-O (Lg3-O) mutation disrupts leaf development at the ligular region of the leaf midrib by transforming blade to sheath. In a previous study, we showed that leaf sectors of Lg3 mutant activity are cell nonautonomous in the transverse dimension and can confer several alternative developmental fates (Fowler, Muehlbauer and Freeling (1996) Genetics 143, 489–503). In our present study we identify five Lg3 sector types in the leaf: sheath-like with displaced ligule (sheath-like), sheath-like with ectopic ligule (ectopic ligule), auricle-like, macro-hairless blade and wild-type blade. The acquisition of a specific sector fate depends on the timing of Lg3 expression. Early Lg3 expression results in adoption of the sheath-like phenotype at the ligule position (a proximal cell fate), whereas later Lg3 expression at the same position results in one of the more distal cell fates. Furthermore, sheath-like Lg3 sectors exhibit a graded continuum of phenotypes in the transformed blade region from the most proximal (sheath) to the most distal (wild-type blade), suggesting that cell fate acquisition is a gradual process. We propose a model for leaf cell fate acquisition based on a timing mechanism whereby cells of the leaf primordium progress through a maturation schedule of competency stages which eventually specify the cell types along the proximal to distal axis of the leaf. In addition, the lateral borders between Lg3 ‘on’ sectors and wild-type leaf sometimes provide evidence of no spreading of the transformed phenotype. In these cases, competency stages are inherited somatically.

Misexpression of basic helix-loop-helix genes in the murine cerebral cortex affects cell fate choices and neuronal survival

Development ◽  
2000 ◽  
Vol 127 (14) ◽  
pp. 3021-3030 ◽  
Author(s):  
L. Cai ◽  
E.M. Morrow ◽  
C.L. Cepko
Keyword(s):  
Cerebral Cortex ◽  
Cell Fate ◽  
Neuronal Survival ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Infected Cells ◽  
Glial Fate

To investigate the role(s) of basic helix-loop-helix genes (bHLH) genes in the developing murine cerebral cortex, Mash1, Math2, Math3, Neurogenin1 (Ngn1), Ngn2, NeuroD, NeuroD2 and Id1 were transduced in vivo into the embryonic and postnatal cerebral cortex using retrovirus vectors. The morphology and location of infected cells were analyzed at postnatal stages. The data indicate that a subset of bHLH genes are capable of regulating the choice of neuronal versus glial fate and that, when misexpressed, they can be deleterious to the survival of differentiating neurons, but not glia.

A novel basic helix–loop–helix (bHLH) transcriptional repressor, NeuroAB, expressed in bipolar and amacrine cells in the chick retina

2004 ◽  
Vol 128 (1) ◽  
pp. 58-74 ◽  
Author(s):  
Takeshi Ohkawara ◽  
Takafumi Shintani ◽  
Chika Saegusa ◽  
Junichi Yuasa-Kawada ◽  
Masakazu Takahashi ◽  
...  
Keyword(s):  
Transcriptional Repressor ◽  
Amacrine Cells ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Chick Retina

scholarly journals The Drosophila Basic Helix-Loop-Helix Protein DIMMED Directly Activates PHM, a Gene Encoding a Neuropeptide-Amidating Enzyme

2007 ◽  
Vol 28 (1) ◽  
pp. 410-421 ◽  
Author(s):  
Dongkook Park ◽  
Orie T. Shafer ◽  
Stacie P. Shepherd ◽  
Hyunsuk Suh ◽  
Jennifer S. Trigg ◽  
...  
Keyword(s):  
Cell Fate ◽  
Transcriptional Activation ◽  
Regulatory Region ◽  
Total Activity ◽  
Bhlh Protein ◽  
Hek 293 ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
E Boxes

ABSTRACT The basic helix-loop-helix (bHLH) protein DIMMED (DIMM) supports the differentiation of secretory properties in numerous peptidergic cells of Drosophila melanogaster. DIMM is coexpressed with diverse amidated neuropeptides and with the amidating enzyme peptidylglycine α-hydroxylating monooxygenase (PHM) in approximately 300 cells of the late embryo. Here we confirm that DIMM has transcription factor activity in transfected HEK 293 cells and that the PHM gene is a direct target. The mammalian DIMM orthologue MIST1 also transactivated the PHM gene. DIMM activity was dependent on the basic region of the protein and on the sequences of three E-box sites within PHM's first intron; the sites make different contributions to the total activity. These data suggest a model whereby the three E boxes interact cooperatively and independently to produce high PHM transcriptional activation. This DIMM-controlled PHM regulatory region displayed similar properties in vivo. Spatially, its expression mirrored that of the DIMM protein, and its activity was largely dependent on dimm. Further, in vivo expression was highly dependent on the sequences of the same three E boxes. This study supports the hypothesis that DIMM is a master regulator of a peptidergic cell fate in Drosophila and provides a detailed transcriptional mechanism of DIMM action on a defined target gene.

EGF receptor attenuates Dpp signaling and helps to distinguish the wing and leg cell fates in Drosophila

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3769-3776 ◽  
Author(s):  
K. Kubota ◽  
S. Goto ◽  
K. Eto ◽  
S. Hayashi
Keyword(s):  
Spatial Distribution ◽  
Cell Fate ◽  
Receptor Tyrosine Kinase ◽  
Egf Receptor ◽  
Homeobox Gene ◽  
Cell Fate Decision ◽  
Cell Fates ◽  
Dorsoventral Axis ◽  
Fate Decision ◽  
Number Of Cells

Wing and leg precursors of Drosophila are recruited from a common pool of ectodermal cells expressing the homeobox gene Dll. Induction by Dpp promotes this cell fate decision toward the wing and proximal leg. We report here that the receptor tyrosine kinase EGFR antagonizes the wing-promoting function of Dpp and allows recruitment of leg precursor cells from uncommitted ectodermal cells. By monitoring the spatial distribution of cells responding to Dpp and EGFR, we show that nuclear transduction of the two signals peaks at different position along the dorsoventral axis when the fates of wing and leg discs are specified and that the balance of the two signals assessed within the nucleus determines the number of cells recruited to the wing. Differential activation of the two signals and the cross talk between them critically affect this cell fate choice.

Roles of homeobox and bHLH genes in specification of a retinal cell type

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1313-1322 ◽  
Author(s):  
J. Hatakeyama ◽  
K. Tomita ◽  
T. Inoue ◽  
R. Kageyama
Keyword(s):  
Cell Fate ◽  
Bipolar Cell ◽  
Homeobox Gene ◽  
Bipolar Cells ◽  
Inner Nuclear Layer ◽  
Muller Glia ◽  
Müller Glia ◽  
Bhlh Genes ◽  
Glial Fate ◽  
Cell Genesis

Previous analysis of mutant mice has revealed that the bHLH genes Mash1 and Math3, and the homeobox gene Chx10 are essential for generation of bipolar cells, the interneurons present in the inner nuclear layer of the retina. Thus, a combination of the bHLH and homeobox genes should be important for bipolar cell genesis, but the exact functions of each gene remain largely unknown. We have found that in Mash1-Math3 double-mutant retina, which exhibits a complete loss of bipolar cells, Chx10 expression did not disappear but remained in Muller glial cells, suggesting that Chx10 expression per se is compatible with gliogenesis. In agreement with this, misexpression of Chx10 alone with retrovirus in the retinal explant cultures induced generation of the inner nuclear layer cells, including Muller glia, but few of them were mature bipolar cells. Misexpression of Mash1 or Math3 alone did not promote bipolar cell genesis either, but inhibited Muller gliogenesis. In contrast, misexpression of Mash1 or Math3 together with Chx10 increased the population of mature bipolar cells and decreased that of Muller glia. Thus, the homeobox gene provides the inner nuclear layer-specific identity while the bHLH genes regulate the neuronal versus glial fate determination, and these two classes of genes together specify the bipolar cell fate. Moreover, Mash1 and Math3 promoted the bipolar cell fate, but not the other inner nuclear layer-specific neuronal subtypes in the presence of Chx10, raising the possibility that the bHLH genes may be involved in neuronal subtype specification, in addition to simply making the neuronal versus glial fate choice.

Phosphorylation of basic helix–loop–helix transcription factor Twist in development and disease

2012 ◽  
Vol 40 (1) ◽  
pp. 90-93 ◽  
Author(s):  
Gongda Xue ◽  
Brian A. Hemmings
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Cancer Progression ◽  
Tumour Growth ◽  
Differential Regulation ◽  
Signalling Pathways ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Recent Advances ◽  
Secondary Tumour

The transcription factor Twist plays vital roles during embryonic development through regulating/controlling cell migration. However, postnatally, in normal physiological settings, Twist is either not expressed or inactivated. Increasing evidence shows a strong correlation between Twist reactivation and both cancer progression and malignancy, where the transcriptional activities of Twist support cancer cells to disseminate from primary tumours and subsequently establish a secondary tumour growth in distant organs. However, it is largely unclear how this signalling programme is reactivated or what signalling pathways regulate its activity. The present review discusses recent advances in Twist regulation and activity, with a focus on phosphorylation-dependent Twist activity, potential upstream kinases and the contribution of these factors in transducing biological signals from upstream signalling complexes. The recent advances in these areas have shed new light on how phosphorylation-dependent regulation of the Twist proteins promotes or suppresses Twist activity, leading to differential regulation of Twist transcriptional targets and thereby influencing cell fate.

scholarly journals BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Richard H Row ◽  
Amy Pegg ◽  
Brian A Kinney ◽  
Gist H Farr ◽  
Lisa Maves ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bhlh Transcription Factor ◽  
Germ Layer ◽  
Transcription Factor Activity ◽  
Fgf Signaling ◽  
Factor Activity ◽  
Cell Fates ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Transcription Factors

The mesodermal germ layer is patterned into mediolateral subtypes by signaling factors including BMP and FGF. How these pathways are integrated to induce specific mediolateral cell fates is not well understood. We used mesoderm derived from post-gastrulation neuromesodermal progenitors (NMPs), which undergo a binary mediolateral patterning decision, as a simplified model to understand how FGF acts together with BMP to impart mediolateral fate. Using zebrafish and mouse NMPs, we identify an evolutionarily conserved mechanism of BMP and FGF-mediated mediolateral mesodermal patterning that occurs through modulation of basic helix-loop-helix (bHLH) transcription factor activity. BMP imparts lateral fate through induction of Id helix loop helix (HLH) proteins, which antagonize bHLH transcription factors, induced by FGF signaling, that specify medial fate. We extend our analysis of zebrafish development to show that bHLH activity is responsible for the mediolateral patterning of the entire mesodermal germ layer.

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