Mutually Repressive Transcription Factors Drive Intestinal Maturation for Weaning

Abstract

In mammals, rapid neonatal growth depends on specialized intestinal enterocytes that absorb nutrients from milk. These cells exhibit distinct functions, morphologies, and gene expression programs that support neonatal nutrition before transitioning to an adult state at weaning. However, the transcriptional mechanisms that establish neonatal enterocyte identity and coordinate their maturation remain poorly understood. Here we show that the transcription factors BLIMP1 and CASZ1 form a central switch in the timing of enterocyte maturation. While BLIMP1 marks and promotes neonatal enterocytes, CASZ1 is expressed in adult enterocytes and is required for the proper timing of their emergence. Genetic analysis indicates that these neonatal and adult factors are mutually repressive, forming a genetic switch underlying weaning. This regulatory mechanism also controls glucocorticoid-induced maturation, a process relevant to both normal weaning and the clinical use of corticosteroids to promote epithelial maturation in preterm infants. We show that corticosteroids act directly on the intestinal epithelium and require CASZ1 to induce maturation. Together, these findings reveal a transcriptional mechanism that coordinates intestinal epithelial identity with the changing nutritional demands of early life and mediates the response to maturation-promoting hormones.

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BibTeX RIS

BibTeX

@misc{scales2026mutually,
  title = {{Mutually Repressive Transcription Factors Drive Intestinal Maturation for Weaning}},
  author = {M. K. Scales and R. Karsan and J. Underwood and A. M. Bara and Y. Wang and K. Sumigray and T. Lechler},
  howpublished = {bioRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.04.764083},
  url = {https://www.biorxiv.org/content/10.64898/2026.11.04.764083v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Mutually Repressive Transcription Factors Drive Intestinal Maturation for Weaning
AU  - M. K. Scales
AU  - R. Karsan
AU  - J. Underwood
AU  - A. M. Bara
AU  - Y. Wang
AU  - K. Sumigray
AU  - T. Lechler
PY  - 2026
DA  - 2026/11/04
PB  - bioRxiv
DO  - 10.64898/2026.11.04.764083
UR  - https://www.biorxiv.org/content/10.64898/2026.11.04.764083v1
AB  - In mammals, rapid neonatal growth depends on specialized intestinal enterocytes that absorb nutrients from milk. These cells exhibit distinct functions, morphologies, and gene expression programs that support neonatal nutrition before transitioning to an adult state at weaning. However, the transcriptional mechanisms that establish neonatal enterocyte identity and coordinate their maturation remain poorly understood. Here we show that the transcription factors BLIMP1 and CASZ1 form a central switch in the timing of enterocyte maturation. While BLIMP1 marks and promotes neonatal enterocytes, CASZ1 is expressed in adult enterocytes and is required for the proper timing of their emergence. Genetic analysis indicates that these neonatal and adult factors are mutually repressive, forming a genetic switch underlying weaning. This regulatory mechanism also controls glucocorticoid-induced maturation, a process relevant to both normal weaning and the clinical use of corticosteroids to promote epithelial maturation in preterm infants. We show that corticosteroids act directly on the intestinal epithelium and require CASZ1 to induce maturation. Together, these findings reveal a transcriptional mechanism that coordinates intestinal epithelial identity with the changing nutritional demands of early life and mediates the response to maturation-promoting hormones.
ER  -

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