Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm

Abstract

Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidney by restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and hand2 promotes venous development while inhibiting IM formation at this interface. Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development. Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM.DOI: http://dx.doi.org/10.7554/eLife.19941.001

A show of Hands: Novel and conserved expression patterns of teleost hand paralogs during craniofacial, heart, fin, peripheral nervous system and gut development

“…This Caz hand1 expression resembles that of hand2 in the zebrafish posterior LPM, where hand2 regulates the size of the intermediate mesoderm. 31 Our results show that the expression of hand1, but not hand2, in the cichlid LPM differs from mouse or zebrafish Hand gene expression, in which hand2, but not hand1, is expressed in the LPM. 8,18,19,27 The lack of hand2 expression in cichlid LPM is consistent with previous reports in teleosts with a two hand gene complement.…”

“…6,30 Mouse Hand2, but not Hand1, is expressed in the LPM. 8,18,19 Similarly hand2 is expressed in the zebrafish LPM, 27,31 while it is not expressed in the LPM of teleosts with two hand genes in their genomes, such as medaka and Nile tilapia. 32 Because of the close evolutionary relationship between Caz and Nile tilapia, we expected Caz hand2 expression to be absent from the LPM, while hand1 expression in this species remained to be determined.…”

Transcriptional activity of Npas4l controls endothelial lineage specification and restriction in zebrafish

“…However, endothelial lineage specification defects leading to an increase in the number of pronephric tubule cells have been previously observed in hand2 mutants (Perens et al, 2016) and in tbx16 mutants (Rohde et al, 2004). Both hand2 and tbx16 mutants display a reduction in tal1 expression (Rohde et al, 2004;Warga et al, 2013;Perens et al, 2016). Moreover, overexpression of either tal1 (Gering et al, 2003) or hand2 (Perens et al, 2016) caused a reduction in the size of the pronephric tubules and an increase in the number of endothelial cells.…”

“…This phenotype is not observed in etsrp mutants. However, endothelial lineage specification defects leading to an increase in the number of pronephric tubule cells have been previously observed in hand2 mutants (Perens et al, 2016) and in tbx16 mutants (Rohde et al, 2004). Both hand2 and tbx16 mutants display a reduction in tal1 expression (Rohde et al, 2004;Warga et al, 2013;Perens et al, 2016).…”

“…The lateral plate mesoderm itself gives rise to progenitors of myeloid, cardiopharyngeal, intestinal smooth muscle, pectoral fin, endothelial and blood progenitors (Prummel et al 2019, Figure 1.2). Whether pax2a positive pronephric mesoderm should be considered to be a lateral plate mesoderm-derived (Prummel et al, 2019) or an intermediate mesoderm-derived (Perens et al, 2016) cell population is debated. Although the lateral plate mesoderm is the main origin of endothelial cells in zebrafish, other mesodermal sources of specialized endothelial cells exist.…”