Kcnip1 a Ca2+-dependent transcriptional repressor regulates the size of the neural plate in Xenopus

Abstract

In amphibian embryos, our previous work has demonstrated that calcium transients occurring in the dorsal ectoderm at the onset of gastrulation are necessary and sufficient to engage the ectodermal cells into a neural fate by inducing neural specific genes. Some of these genes are direct targets of calcium. Here we search for a direct transcriptional mechanism by which calcium signals are acting. The only known mechanism responsible for a direct action of calcium on gene transcription involves an EF-hand Ca²⁺ binding protein which belongs to a group of four proteins (Kcnip1 to 4). Kcnip protein can act in a Ca²⁺-dependent manner as a transcriptional repressor by binding to a specific DNA sequence, the Downstream Regulatory Element (DRE) site. In Xenopus, among the four kcnips, we show that only kcnip1 is timely and spatially present in the presumptive neural territories and is able to bind DRE sites in a Ca²⁺-dependent manner. The loss of function of kcnip1 results in the expansion of the neural plate through an increased proliferation of neural progenitors. Later on, this leads to an impairment in the development of anterior neural structures. We propose that, in the embryo, at the onset of neurogenesis Kcnip1 is the Ca²⁺-dependent transcriptional repressor that controls the size of the neural plate. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.

Nucleotide receptor P2RY4 is required for head formation via induction and maintenance of head organizer in Xenopus laevis

“…Therefore, we speculate that the activated P2RY4 receptor may function to induce the expression of head organizer genes via the increase of [Ca 2+ ]i. Furthermore, xprmt1b , a Xenopus homolog of mammalian arginine methyltransferase prmt1 , was responsive to Ca 2+ increase and expressed in prospective neural territories (Batut et al., ; Neant et al., ). Xprmt1b expression mediating DSCC affected the expression of neural precursor marker zic3 .…”

La saga de l’induction neurale : presque un siècle de recherche

“…Il faut noter que des sites DRE ont été identifiés sur les promoteurs des gènes proneuraux prmt1b et sox2. Ainsi, dans l'ectoderme, en l'absence de signaux Ca 2+ , la protéine KCNIP1 est présente sur les sites DRE, empêchant la transcription des gènes neuraux prmt1b et sox2 [40] ( Figure 5).…”

Ca2+-Dependent Transcriptional Repressors KCNIP and Regulation of Prognosis Genes in Glioblastoma

“…In the fish Danio rerio , the embryonic expressions of kcnip1b and kcnip3 are not detectable before somitogenesis (Stetsyuk et al, 2007) and in the amphibian Xenopus laevis among the four kcnip s, only kcnip1 is expressed at all developmental stages, from fertilized egg to the tadpole stages. By contrast, the transcripts for kcnip2 , kcnip3 , and kcnip4 are expressed at later stages, after the specification of neural territories (Néant et al, 2015).…”

“…Its transcripts are timely and spatially present in the presumptive neural territories. In this in vivo model, loss of function experiments indicate that Kcnip1 is a Ca 2+ -dependent transcriptional repressor that controls the size of the neural plate by regulating the proliferation of neural progenitors (Néant et al, 2015).…”