A Sox Transcription Factor Is a Critical Regulator of Adult Stem Cell Proliferation in the Drosophila Intestine

Abstract

Adult organs and their resident stem cells are constantly facing the challenge of adapting cell proliferation to tissue demand, particularly in response to environmental stresses. Whereas most stress-signaling pathways are conserved between progenitors and differentiated cells, stem cells have the specific ability to respond by increasing their proliferative rate, using largely unknown mechanisms. Here, we show that a member of the Sox family of transcription factors in Drosophila, Sox21a, is expressed in intestinal stem cells (ISCs) in the adult gut. Sox21a is essential for the proliferation of these cells during both normal epithelium turnover and repair. Its expression is induced in response to tissue damage, downstream of the Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways, to promote ISC proliferation. Although short-lived, Sox21a mutant flies show no developmental defects, supporting the notion that this factor is a specific regulator of adult stem cell proliferation.

Intestinal stem cell response to injury: lessons from Drosophila

“…The Sox family member Sox21a is specifically expressed in midgut progenitors but is required specifically in ISCs to promote their proliferation in the posterior midgut [88, 89]. Sox21a expression is upregulated in response to stress and transgenic overexpression of Sox21a in progenitor cells is sufficient to drive ISC proliferation [88].…”

“…Sox21a expression is upregulated in response to stress and transgenic overexpression of Sox21a in progenitor cells is sufficient to drive ISC proliferation [88]. Sox21a is regulated by the AP1 family of transcription factor Fos, which is activated by both JNK and EGFR pathways [88].…”

“…Sox21a expression is upregulated in response to stress and transgenic overexpression of Sox21a in progenitor cells is sufficient to drive ISC proliferation [88]. Sox21a is regulated by the AP1 family of transcription factor Fos, which is activated by both JNK and EGFR pathways [88]. Furthermore, Sox21a is require for ISC overproliferation induced by these pathways [88], suggesting that Sox21a is a common mediator of JNK and EGFR pathways in the regulation of ISC proliferation (Fig.…”

“…Sox21a is regulated by the AP1 family of transcription factor Fos, which is activated by both JNK and EGFR pathways [88]. Furthermore, Sox21a is require for ISC overproliferation induced by these pathways [88], suggesting that Sox21a is a common mediator of JNK and EGFR pathways in the regulation of ISC proliferation (Fig. 3).…”

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

“…It is knowledgeable that adhesion, proliferation [53][54][55] , migration [56] and autophagy [57,58] are the characteristics of cells [59][60][61] . [61] .…”