The secreted BMP antagonist ERFE is required for the development of a functional circulatory system in Xenopus.

The hormone Erythroferrone (ERFE) is a member of the C1q/TNF-related protein family that regulates iron homeostasis through the suppression of hamp. In a gain of function screen in Xenopus embryos, we identified ERFE as a potent secondary axis-inducing agent. Experiments in Xenopus embryos and ectodermal explants revealed that ERFE functions as a selective inhibitor of the BMP pathway and the conserved C1q domain is not required for this activity.

Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA.

In humans, many cases of congenital insensitivity to pain (CIP) are caused by mutations of components of the NGF/TrkA signaling pathway, which is required for survival and specification of nociceptors and plays a major role in pain processing. Mutations in PRDM12 have been identified in CIP patients that indicate a putative role for this transcriptional regulator in pain sensing. Here, we show that Prdm12 expression is restricted to developing and adult nociceptors and that its genetic ablation compromises their viability and maturation.

DMRT5, DMRT3, and EMX2 Cooperatively Repress at the Pallium-Subpallium Boundary to Maintain Cortical Identity in Dorsal Telencephalic Progenitors.

Specification of dorsoventral regional identity in progenitors of the developing telencephalon is a first pivotal step in the development of the cerebral cortex and basal ganglia. Previously, we demonstrated that the two zinc finger and () genes, () and , which are coexpressed in high caudomedial to low rostrolateral gradients in the cerebral cortical primordium, are separately needed for normal formation of the cortical hem, hippocampus, and caudomedial neocortex. We have now addressed the role of and in controlling dorsoventral division of the telencephalon in mice of either sex by comparing the phenotypes of single knock-out (KO) with double KO embryos and by misexpressing in the ventral telencephalon.

Divergent axial morphogenesis and early expression in vertebrate prospective floor plate.

Background: The notochord has organizer properties and is required for floor plate induction and dorsoventral patterning of the neural tube. This activity has been attributed to sonic hedgehog (shh) signaling, which originates in the notochord, forms a gradient, and autoinduces expression in the floor plate. However, reported data are inconsistent and the spatiotemporal development of the relevant expression domains has not been studied in detail.

Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus.

V1 interneurons are inhibitory neurons that play an essential role in vertebrate locomotion. The molecular mechanisms underlying their genesis remain, however, largely undefined. Here, we show that the transcription factor Prdm12 is selectively expressed in p1 progenitors of the hindbrain and spinal cord in the frog embryo, and that a similar restricted expression profile is observed in the nerve cord of other vertebrates as well as of the cephalochordate amphioxus.

YAP controls retinal stem cell DNA replication timing and genomic stability.

The adult frog retina retains a reservoir of active neural stem cells that contribute to continuous eye growth throughout life. We found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in these stem cells. Yap knock-down leads to an accelerated S-phase and an abnormal progression of DNA replication, a phenotype likely mediated by upregulation of c-Myc.

Dlk1 promotes a fast motor neuron biophysical signature required for peak force execution.

Motor neurons, which relay neural commands to drive skeletal muscle movements, encompass types ranging from "slow" to "fast," whose biophysical properties govern the timing, gradation, and amplitude of muscle force. Here we identify the noncanonical Notch ligand Delta-like homolog 1 (Dlk1) as a determinant of motor neuron functional diversification. Dlk1, expressed by ~30% of motor neurons, is necessary and sufficient to promote a fast biophysical signature in the mouse and chick.

The Prdm13 histone methyltransferase encoding gene is a Ptf1a-Rbpj downstream target that suppresses glutamatergic and promotes GABAergic neuronal fate in the dorsal neural tube.

The basic helix-loop-helix (bHLH) transcriptional activator Ptf1a determines inhibitory GABAergic over excitatory glutamatergic neuronal cell fate in progenitors of the vertebrate dorsal spinal cord, cerebellum and retina. In an in situ hybridization expression survey of PR domain containing genes encoding putative chromatin-remodeling zinc finger transcription factors in Xenopus embryos, we identified Prdm13 as a histone methyltransferase belonging to the Ptf1a synexpression group. Gain and loss of Ptf1a function analyses in both frog and mice indicates that Prdm13 is positively regulated by Ptf1a and likely constitutes a direct transcriptional target.

NumbL is essential for Xenopus primary neurogenesis.

Background: Members of the vertebrate Numb family of cell fate determinants serve multiple functions throughout early embryogenesis, including an essential role in the development of the nervous system. The Numb proteins interact with various partner proteins and correspondingly participate in multiple cellular activities, including inhibition of the Notch pathway.

Results: Here, we describe the expression characteristics of Numb and Numblike (NumbL) during Xenopus development and characterize the function of NumbL during primary neurogenesis.

Scratch2 modulates neurogenesis and cell migration through antagonism of bHLH proteins in the developing neocortex.

Scratch genes (Scrt) are neural-specific zinc-finger transcription factors (TFs) with an unknown function in the developing brain. Here, we show that, in addition to the reported expression of mammalian Scrt2 in postmitotic differentiating and mature neurons in the developing and early postnatal brain, Scrt2 is also localized in subsets of mitotic and neurogenic radial glial (RGP) and intermediate (IP) progenitors, as well as in their descendants-postmitotic IPs and differentiating neurons at the border subventricular/intermediate zone. Conditional activation of transgenic Scrt2 in cortical progenitors in mice promotes neuronal differentiation by favoring the direct mode of neurogenesis of RGPs at the onset of neurogenesis, at the expense of IP generation.

Comparative expression analysis of the neurogenins in Xenopus tropicalis and Xenopus laevis.

The Neurogenin (Ngn 1-3) family of proneural basic helix-loop-helix (bHLH) transcription factors are key regulators of vertebrate neurogenesis. In the developing vertebrate nervous system, the Ngns are essential for the commitment to a neuronal fate and participate in the specification of neuronal cell-type identity. Xenopus laevis is widely used as a model system to study the early events of vertebrate neurogenesis, however, only Ngnr-1, which is most closely related to the mammalian Ngn2, has been described and characterized.

The RNA-binding protein XSeb4R: a positive regulator of VegT mRNA stability and translation that is required for germ layer formation in Xenopus.

VegT represents a localized maternal determinant essentially required for endoderm formation in Xenopus. Here, we report on the identification of the RNA-binding protein XSeb4R as a positive regulator of VegT. XSeb4R interacts directly with the 3'-untranslated region of VegT mRNA, stabilizes it, and stimulates translation.

Ptf1a triggers GABAergic neuronal cell fates in the retina.

Background: In recent years, considerable knowledge has been gained on the molecular mechanisms underlying retinal cell fate specification. However, hitherto studies focused primarily on the six major retinal cell classes (five types of neurons of one type of glial cell), and paid little attention to the specification of different neuronal subtypes within the same cell class. In particular, the molecular machinery governing the specification of the two most abundant neurotransmitter phenotypes in the retina, GABAergic and glutamatergic, is largely unknown.

Expression and regulation of Xenopus CRMP-4 in the developing nervous system.

The collaspin response mediator proteins (CRMPs) are a family of cytosolic phosphoproteins which play a critical role in the establishment of neuronal polarity and growth cone guidance. Here, we describe the temporal and spatial expression of CRMP-4 during early Xenopus embryogenesis. CRMP-4 transcripts were first detected by whole mount in situ hybridization at the end of gastrulation in the prospective neuroectoderm.

Mxi1 is essential for neurogenesis in Xenopus and acts by bridging the pan-neural and proneural genes.

We have isolated and characterized Xenopus Mxi1, a member of the Myc/Max/Mad family of bHLHZip transcription factors. Xmxi1 transcripts are present during gastrulation and early neurula stages, earlier and in broader domains as compared to the neuronal determination factor neurogenin (X-ngnr-1). Consistent with an early role in neurogenesis, Xmxi1 is positively regulated by Sox3, SoxD, and proneural genes, as well as negatively by the Notch pathway.

I-SceI meganuclease-mediated transgenesis in Xenopus.

Several experimental approaches have been described to generate transgenic frogs. Here, we report on the application of a novel method in Xenopus, making use of I-SceI meganuclease. The characteristic feature of this endonuclease is that it has an extended recognition site of 18 bp, which is expected to exist only once in 7 x 10(10) bp of random DNA sequences.

Isolation and comparative expression analysis of the Myc-regulatory proteins Mad1, Mad3, and Mnt during Xenopus development.

The Myc-Max-Mad network of transcription factors plays an essential role in many cellular processes such as proliferation, differentiation, and apoptosis. The Mad proteins heterodimerize with Max, function as transcriptional repressors, and are capable of antagonizing the transforming activity of Myc. We report on the isolation of Xmad1, Xmad3, and Xmnt, novel Xenopus genes belonging to the Mad family.

Isolation and characterization of the Xenopus HIVEP gene family.

The HIVEP gene family encodes for very large sequence-specific DNA binding proteins containing multiple zinc fingers. Three mammalian paralogous genes have been identified, HIVEP1, -2 and -3, as well as the closely related Drosophila gene, Schnurri. These genes have been found to directly participate in the transcriptional regulation of a variety of genes.

Autoregulation of Xvent-2B; direct interaction and functional cooperation of Xvent-2 and Smad1.

Members of the Xvent-2 homeodomain transcription factor family are immediate response genes of BMP-4 signaling. The bone morphogenetic protein response element (BRE) of Xvent-2B was previously identified and characterized with respect to Smad1 and Smad4 binding sites. In this study, we further report on the transcriptional regulation of Xvent-2B.