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New ingredients for old recipes - Nature.com

The pancreas is an essential organ present in all vertebrates, and human pancreatic agenesis is an extremely rare disorder of largely unknown genetic determinants. A study now demonstrates that a primate-specific regulatory network controlled by the KRAB zinc-finger protein ZNF808 is essential for pancreas development.

Embryonic development relies on the establishment of proper spatiotemporal gene expression programs, ensuring timely cell positioning and acquisitions of cell fate. Such gene regulatory networks (GRNs) are orchestrated by DNA-binding operators known as transcription factors, which coordinate the cis-regulatory activities of thousands of genomic loci, including promoter and enhancer regions, in one go. Mammalian embryogenesis is a prime example of a complex and constrained developmental process that enables a single fertilized egg to develop into an embryo composed of an intricate mixture of cell fates and identities, beautifully organized into specialized tissues and organs. The fields of evolutionary developmental biology and comparative embryology highlighted deep developmental homologies in mammalian development but also identified species-specific traits in ontogenesis, which suggests that a conserved genetic toolkit is modulated by species-restricted transcription factors and GRNs. Therefore, although the building bricks seem to be the same across long evolutionary time periods, species-specific cis-regulatory activities and trans-acting factors contribute to the tinkering of highly constrained molecular processes. Among the possible vectors of cis-regulatory novelty, transposable elements, also known as mobile genetic elements, emerge as a dominant force that has extensively shaped extant mammalian genomes1. Around five million transposons and transposon-like repetitive elements contribute to more than half of the human genome sequence; only a minute fraction (~1:4,000) is still capable of spreading, all other elements have lost this potential owing to genetic drift2.

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Fig. 1: ZNF808 mutation leads to pancreatic agenesis.

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Author notes

  1. These authors contributed equally: Olga Rosspopoff, Filipe Martins.

Authors and Affiliations

  1. School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

    Olga Rosspopoff, Filipe Martins & Didier Trono

Authors
  1. Olga Rosspopoff
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  2. Filipe Martins
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  3. Didier Trono
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Correspondence to Didier Trono.

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The authors declare no competing interests.

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Rosspopoff, O., Martins, F. & Trono, D. New ingredients for old recipes. Nat Genet (2023). https://ift.tt/JbKsnH3

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