Congenital defects in genital and/or gonadal development occur in 1 in 1000 humans, but the molecular basis for these defects in most cases remains undefined. We show that the basic helix-loop-helix transcription factor Pod1(capsulin/epicardin/Tcf21) is essential for normal development of the testes and ovaries, and hence for sexual differentiation. The gonads of Pod1knockout (KO) mice were markedly hypoplastic, and the urogenital tracts of both XX and XY mice remained indistinguishable throughout embryogenesis. Within Pod1 KO gonads, the number of cells expressing the cholesterol side-chain cleavage enzyme (Scc) was increased markedly. Biochemical and genetic approaches demonstrated that Pod1 transcriptionally represses steroidogenic factor 1 (Sf1/Nr5a1/Ad4BP), an orphan nuclear receptor that regulates the expression of multiple genes (including Scc) that mediate sexual differentiation. Our results establish that Pod1 is essential for gonadal development, and place it in a transcriptional network that orchestrates cell fate decisions in gonadal progenitors.
History of our journals
As our publisher, The Company of Biologists, turns 100 years old, read about Development’s journey and highlights from some its first issues, and explore the history of each of our sister journals: Journal of Cell Science, Journal of Experimental Biology, Disease Models & Mechanisms and Biology Open.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues
Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 15 May 2025.
A case for broadening our view of mechanism in developmental biology
In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
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