Biology subjects

Yelon, D.

Publications and source records attributed to Yelon, D..

7 recordsLinked to original sources

bioRxiv2026

twist1a and twist1b play overlapping roles during zebrafish pectoral fin development

Background: In humans, haploinsufficiency of TWIST1 leads to Saethre-Chotzen Syndrome, characterized by limb abnormalities and craniofacial defects. In mouse, Twist1 promotes limb bud outgrowth via maintenance of the apical ectodermal ridge (AER), in addition to its craniofacial roles. In zebrafish, two twist1 paralogs, twist1a and twist1b, are known to influence cranial neural crest and cranial suture development but have not yet been implicated in limb formation. Results: We find that twist1a and twist1b act redundantly during zebrafish pectoral fin development. While twist1b mutants have normal fins, twist1a mutants have small fins, and twist1a;twist1b double mutants lack fins. These defects appear to originate with impaired establishment of the pectoral fin field, followed by failure of AER formation, likely due to reduced fgf10a expression in the fin mesenchyme. Anterior-posterior patterning of the fin bud is relatively normal in twist1a mutants and twist1a;twist1b double mutants, albeit with an anterior extension of shha expression in some embryos. Conclusions: Together, our results show that twist1a and twist1b play crucial and overlapping roles in zebrafish pectoral fin development, echoing roles played by Twist1 in the mouse limb bud and highlighting an early impact of twist1 genes on the initial formation of the zebrafish forelimb field.

developmental biology↗

bioRxiv2025

Hedgehog and Bmp signaling pathways play opposing roles during establishment of the cardiac inflow tract in zebrafish

Cardiac pacemaking activity is controlled by specialized cardiomyocytes in the cardiac inflow tract (IFT), but the processes that determine IFT dimensions remain poorly understood. Here, we show that Hedgehog (Hh) signaling limits the number of IFT cardiomyocytes in the embryonic zebrafish heart. Inhibiting Hh signaling, either genetically or pharmacologically, results in an expanded IFT population. In contrast, reducing Bmp signaling decreases the number of IFT cardiomyocytes, while increasing Bmp signaling leads to an excess of IFT cardiomyocytes. Temporal inhibition of each pathway reveals that Hh and Bmp signaling act before myocardial differentiation to regulate IFT size. Simultaneous reduction of both Hh and Bmp signaling yields a relatively normal number of IFT cardiomyocytes, suggesting that these pathways function antagonistically during IFT development. Additionally, epistasis analysis suggests that Bmp signaling acts upstream of Wnt signaling to promote IFT formation, whereas Hh signaling limits IFT size in a Wnt-independent manner. Our results support a model in which Hh signaling restricts the establishment of the IFT progenitor pool, while Bmp signaling drives IFT progenitor specification prior to Wnt-directed IFT differentiation. SUMMARY STATEMENTHedgehog signaling acts prior to myocardial differentiation to restrict the number of inflow tract cardiomyocytes, while Bmp signaling acts during a similar timeframe to promote inflow tract cardiomyocyte formation.

developmental biology↗

bioRxiv2025

Regionalized regulation of actomyosin organization influences cardiomyocyte cell shape changes during chamber curvature formation

Cardiac chambers emerge from a heart tube that balloons and bends to create expanded ventricular and atrial structures, each containing a convex outer curvature (OC) and a recessed inner curvature (IC). The cellular and molecular mechanisms underlying the formation of these characteristic curvatures remain poorly understood. Here, we demonstrate in zebrafish that the initially similar populations of OC and IC ventricular cardiomyocytes diverge in the organization of their actomyosin cytoskeleton and subsequently acquire distinct OC and IC cell shapes. Altering actomyosin dynamics hinders cell shape changes in the OC, and mosaic analyses indicate that actomyosin regulates cardiomyocyte shape in a cell-autonomous manner. Additionally, both biomechanical cues and the transcription factor Tbx5a influence the basal enrichment of actomyosin and squamous cell morphologies in the OC. Together, our findings demonstrate that intrinsic and extrinsic factors intersect to control actomyosin organization in OC cardiomyocytes, which in turn promotes the cell shape changes that accompany curvature morphogenesis.

developmental biology↗

bioRxiv2024

Drivers of Vessel Progenitor Fate Define Intermediate Mesoderm Dimensions by Inhibiting Kidney Progenitor Specification

Proper organ formation depends on the precise delineation of organ territories containing defined numbers of progenitor cells. Kidney progenitors reside in bilateral stripes of posterior mesoderm that are referred to as the intermediate mesoderm (IM). Previously, we showed that the transcription factors Hand2 and Osr1 act to strike a balance between the specification of the kidney progenitors in the IM and the vessel progenitors in the laterally adjacent territory. Recently, the transcription factor Npas4l - an early and essential driver of vessel and blood progenitor formation - was shown to inhibit kidney development. Here we demonstrate how kidney progenitor specification is coordinated by hand2, osr1, and npas4l. We find that npas4l is necessary to inhibit IM formation. Consistent with the expression of npas4l flanking the medial and lateral sides of the IM, our findings suggest roles for npas4l in defining the IM boundaries at each of these borders. At the lateral IM border, hand2 promotes and osr1 inhibits the formation of npas4l-expressing lateral vessel progenitors, and hand2 requires npas4l to inhibit IM formation and to promote vessel formation. Meanwhile, npas4l appears to have an additional role in suppressing IM fate at the medial border: npas4l loss-of-function enhances hand2 mutant IM defects and results in excess IM generated outside of the lateral hand2-expressing territory. Together, our findings reveal that establishment of the medial and lateral boundaries of the IM requires inhibition of kidney progenitor specification by the neighboring drivers of vessel progenitor fate.

developmental biology↗

bioRxiv2023

The MEK-ERK signaling pathway promotes maintenance of cardiac chamber identity

Ventricular and atrial cardiac chambers have unique structural and contractile characteristics that underlie their distinct functions. Intriguingly, the maintenance of chamber-specific features requires active reinforcement, even in differentiated cardiomyocytes. Prior studies in zebrafish have shown that sustained FGF signaling acts upstream of nkx2.5 to maintain ventricular identity, but the rest of this maintenance pathway remains unclear. Here, we show that MEK1/2-ERK1/2 signaling acts downstream of FGF and upstream of nkx2.5 to promote ventricular maintenance. Inhibition of MEK signaling, like inhibition of FGF signaling, results in ectopic atrial gene expression and reduced ventricular gene expression in ventricular cardiomyocytes. FGF and MEK signaling both influence ventricular maintenance over a similar timeframe, when phosphorylated ERK (pERK) is present in the myocardium. However, the role of FGF-MEK activity seems to be context-dependent: some ventricular regions are more sensitive than others to inhibition of FGF-MEK signaling. Additionally, in the atrium, although endogenous pERK does not induce ventricular traits, heightened MEK signaling can provoke ectopic ventricular gene expression. Together, our data reveal chamber-specific roles of MEK-ERK signaling in the maintenance of ventricular and atrial identities. SUMMARY STATEMENTThe MEK-ERK signaling pathway plays distinct roles in the maintenance of ventricular and atrial cardiomyocyte identities.

developmental biology↗

bioRxiv2020

osr1 couples intermediate mesoderm cell fate with temporal dynamics of vessel progenitor cell differentiation

Transcriptional regulatory networks refine gene expression boundaries throughout embryonic development to define the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and its neighboring vessel progenitors are poorly understood. Here, we delineate new roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafish osr1 mutants display decreased IM formation and premature emergence of neighboring lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss of hand2 partially suppresses the osr1 mutant phenotypes. hand2 and osr1 are both expressed in the posterior lateral mesoderm, but osr1 expression decreases dramatically prior to LVP emergence. Overexpressing osr1 inhibits LVP development while enhancing IM formation. Together, our data demonstrate that osr1 modulates both the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels of osr1 and hand2 expression is essential to demarcate the dimensions of kidney and vessel progenitor territories. SUMMARY STATEMENTAnalysis of the osr1 mutant phenotype reveals roles in determining the extent of intermediate mesoderm formation while inhibiting premature differentiation of neighboring vessel progenitors.

developmental biology↗

bioRxiv2019

Cardiac function modulates endocardial cell dynamics to shape the cardiac outflow tract

Physical forces are important participants in the cellular dynamics that shape developing organs. During heart formation, for example, contractility and blood flow generate biomechanical cues that influence patterns of cell behavior. Here, we address the interplay between function and form during the assembly of the cardiac outflow tract (OFT), a crucial connection between the heart and vasculature that develops while circulation is underway. In zebrafish, we find that the OFT expands via accrual of both endocardial and myocardial cells. However, when cardiac function is disrupted, OFT endocardial growth ceases, accompanied by reduced proliferation and reduced addition of cells from adjacent vessels. The TGF{beta} receptor Acvrl1 is required for addition of endocardial cells, but not for their proliferation, indicating distinct regulation of these essential cell behaviors. Together, our results suggest that cardiac function modulates OFT morphogenesis by triggering endocardial cell accumulation that induces OFT lumen expansion and shapes OFT dimensions.

developmental biology↗