Transcriptional regulation of TLX2 and impaired intestinal innervation: Possible role of the PHOX2A and PHOX2B genes

Silvia Borghini, Marco Di Duca, Giuseppe Santamaria, Manuela Vargiolu, Tiziana Bachetti, Francesca Cargnin, Alessio Pini Prato, Roberto De Giorgio, Margherita Lerone, Vincenzo Stanghellini, Vincenzo Jasonni, Diego Fornasari, Roberto Ravazzolo, Isabella Ceccherini

Research output: Contribution to journalArticlepeer-review


TLX2 (also known as HOX11L1, Ncx and Enx) is a transcription factor playing a crucial role in the development of the enteric nervous system, as confirmed by mice models exhibiting intestinal hyperganglionosis and pseudo-obstruction. However, congenital defects of TLX2 have been excluded as a major cause of intestinal motility disorders in patients affected with intestinal neuronal dysplasia (IND) or pseudo-obstruction. After demonstrating the direct regulation of TLX2 expression by the homeoprotein PHOX2B, in the present work, we have focused on its paralogue PHOX2A. By co-transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation, we have demonstrated that PHOX2A, like PHOX2B, is involved in the cascade leading to TLX2 transactivation and presumably in the intestinal neuronal differentiation. Based on the hypothesis that missed activation of the TLX2 gene induces the development of enteric nervous system defects, PHOX2A and PHOX2B have been regarded as novel candidate genes involved in IND and pseudo-obstruction and consequently analyzed for mutations in a specific set of 26 patients. We have identified one still unreported PHOX2A variant; however, absence of any functional effect on TLX2 transactivation suggests that regulators or effectors other than the PHOX2 genes must act in the same pathway, likely playing a non redundant and direct role in the pathogenesis of such enteric disorders.

Original languageEnglish
Pages (from-to)848-855
Number of pages8
JournalEuropean Journal of Human Genetics
Issue number8
Publication statusPublished - Aug 2007

ASJC Scopus subject areas

  • Genetics(clinical)


Dive into the research topics of 'Transcriptional regulation of TLX2 and impaired intestinal innervation: Possible role of the PHOX2A and PHOX2B genes'. Together they form a unique fingerprint.

Cite this