Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm.
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 zebrafishhand2mutants and is diminished whenhand2is overexpressed. Within the posterior mesoderm,hand2is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, andhand2promotes venous development while inhibiting IM formation at this interface. Furthermore,hand2and the co-expressed zinc-finger transcription factorosr1have functionally antagonistic influences on kidney development. Together, our data suggest thathand2functions in opposition toosr1to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM.
Division of Biological Sciences, University of California, San Diego, San Diego, United States.|Department of Pediatrics, School of Medicine, University of California, San Diego, San Diego, United States.
Elliot A
http://orcid.org/0000-0003-3377-7708
EA
Perens
Division of Biological Sciences, University of California, San Diego, San Diego, United States.|Departamento de Ciencias Biológicas, Facultad de Ciencias, Universidad de los Andes, Bogotá, Colombia.
Zayra V
http://orcid.org/0000-0001-5671-7017
ZV
Garavito-Aguilar
Departamento de Ciencias Biológicas, Facultad de Ciencias, Universidad de los Andes, Bogotá, Colombia.
Gina P
http://orcid.org/0000-0003-2156-6209
GP
Guio-Vega
Departamento de Ciencias Biológicas, Facultad de Ciencias, Universidad de los Andes, Bogotá, Colombia.
Karen T
http://orcid.org/0000-0002-6543-5254
KT
Peña
Division of Biological Sciences, University of California, San Diego, San Diego, United States.
Yocheved L
http://orcid.org/0000-0002-4388-9511
YL
Schindler
Division of Biological Sciences, University of California, San Diego, San Diego, United States.
Deborah
http://orcid.org/0000-0003-3523-4053
D
Yelon
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000254:growth & development / Q000378:metabolism*; D008648:Mesoderm / Q000254:growth & development / Q000378:metabolism; D009154:Mutation; D038081:Organogenesis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014680:Veins / Q000254:growth & development / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C533776:Osr1 protein, zebrafish; C410915:hand2 protein, zebrafish
Hand2; Osr1; developmental biology; intermediate mesoderm; organogenesis; pronephron; stem cells; zebrafish