PROX1 is a specific and dynamic marker of sacral neural crest cells in the chicken intestine

Abstract

The Enteric Nervous System (ENS) is a complex network constituted of neurons and glial cells that ensures the intrinsic innervation of the gastrointestinal tract. ENS cells originate from vagal and sacral neural crest cells that are initially located at the border of the neural tube. In birds, sacral neural crest cells (sNCCs) first give rise to an extramural ganglionated structure (the so-called Nerve of Remak (NoR)) and to the pelvic plexus. Later, sNCCs enter the colon mesenchyme to colonize and contribute to the intrinsic innervation of the caudal part of the gut. However, no specific sNCC marker has been described. Here, we report the expression pattern of Prospero-related homeobox 1 (PROX1) in the developing chick colon.PROX1 is a homeobox domain transcription factor that plays a role in cell type specification in various tissues. Using in situ hybridization and immunofluorescence techniques, we showed that PROX1 is expressed in sNCCs localized in the NoR and in the pelvic plexus.Then, using real-time quantitative PCR we found that PROX1 displays a strong and highly dynamic expression pattern during NoR development. Moreover, we demonstrated using in vivo cell tracing, that sNCCs are the source of the PROX1-positive cells within the NoR. Our results indicate that PROX1 is the first marker that specifically identifies sNCCs. This might help to better identify the role of the different neural crest cell populations in distal gut innervation, and consequently to improve the diagnosis of diseases linked to incomplete ENS formation, such as Hirschsprung's disease. KEYWORDS

CircANKRD12/circTIMMDC1 act as miR-181b-5p sponge to synergistically regulate neural cell migration via the PROX1-NOTCH1-HES1 axis in Hirschsprung's disease

“…Likewise, NOTCH1, a member of NOTCH receptors family, was veri ed expressed in ganglia of the submucosal and myenteric plexus in rat and human ENS [23,24,31]. It was reported that increasing NOTCH signaling in NCCs disabled NCC migrating into the ENS [29]. Equally, oversupply of NOTCH in the enteric mesenchyme led to inadequate neural crest-derived cells migration and colonization [30].…”

“…Prominent among these is still the CNS, where NOTCH1 has been implicated in processes ranging from neuron differentiation, proliferation, maturation and colonization. As for ENS, only a few previous studies demonstrated that PROX1 and NOTCH1 were expressed and played a certain role in enteric neuronal cells in several species [29][30][31]. However, what PROX1/NOTCH1 speci c roles involved in ENS and how the upstream mechanisms regulate are remain unclear.…”

Phenotypic switch of smooth muscle cells in paediatric chronic intestinal pseudo‐obstruction syndrome

“…To identify genes that define the SMC immaturity, we screened for genes that demonstrated higher level of expression during the process of SMC differentiation using the chick embryo model. We compared profiles of genes expressed in 6-day-old (E6), a stage in which mesenchymal progenitors are not yet differentiated in SMCs (progenitor stage), to those expressed at E9, a stage in which SMCs are differentiated (differentiated stage) [23][24][25]38 and found Platelet-Derived Growth Factor (PDGF) receptor-alpha (PDGFRA) to be highly expressed in the mesenchymal progenitors (Figure 2A). Its profile contrasts to the ones of SOX10 and RET (Enteric Nervous System (ENS) markers), 23,38 KIT and CD44 (Interstitial Cells of Cajal (ICC) markers), 39,40 and CD34 and WNT5A (telocyte markers) 41,42 and differentiated smooth muscle markers (ACTG2, CNN1, FLNA, MYH11 and TAGLN) that harbour highly expression at differentiated stage (Figure 2A).…”