Biology subjects

Wizenmann, A.

Publications and source records attributed to Wizenmann, A..

6 recordsLinked to original sources

bioRxiv2026

Experimental characterization of chicken OSX/SP7 and embryonic expression analysis reveal skeletal and neural expression domains

The specificity protein 7 (SP7), also known as Osterix (OSX), is a zinc-finger transcription factor essential for osteoblast differentiation and skeletal development. Hereafter, the protein is referred to as OSX/SP7 throughout the manuscript. Although OSX/SP7 has been extensively studied in mammals and teleost fish, its developmental expression pattern in chicken (Gallus gallus) has not been described. Using an experimentally isolated chicken OSX/SP7 sequence, we examined OSX/SP7 mRNA expression during embryogenesis by in situ hybridization. As expected, OSX/SP7 expression was detected in developing skeletal elements undergoing ossification. Unexpectedly, transcripts were also observed in the neuroepithelium, retina, central nervous system, embryonic muscles and integument. Notably, OSX/SP7 expression was present in the neural tube from Hamburger and Hamilton stage 9 and persisted in the developing central nervous system until at least HH40, suggesting that OSX/SP7 functions during avian development may extend beyond osteogenesis. In addition, we reconstructed the chicken OSX/SP7 coding sequence and inferred its associated untranslated regions. The reconstructed ORF was independently supported by maternal and paternal haplotype-resolved chicken genome assemblies and retained the characteristic domain architecture of vertebrate OSX/SP7 proteins despite substantial divergence outside the DNA-binding domain. Taken together, these findings broaden the developmental landscape of OSX/SP7 expression in birds and provide new molecular resources for future studies of OSX/SP7 regulation and function during vertebrate development.

developmental biology↗

bioRxiv2026

The role of the roof plate for mesencephalic trigeminal neuron

The mesencephalic trigeminal nucleus (MTN) contains the proprioceptive sensory neurons that innervate mechanoreceptors in the jaw closing muscles. In the chick embryo, MTN neurons are the first neurons generated in the mesencephalon. They arise bilaterally adjacent to the roof plate and then extend their axons ventrally before projecting caudally towards the rhombencephalon. MTN axons remain in a mid - dorsoventral position and pioneer the lateral longitudinal fasciculus. Notably, MTN axons never cross the roof plate, raising the question of which mechanisms underlie this restriction. Here, we investigated the effects of tissue transplants on the guidance of MTN axons. We found that both the diencephalon and the notochord exert repulsive effects on MTN axons, which could partially explain their early trajectory. We have also analysed the potential roles of the guidance cues BMP2/4, GDF7, SLIT and NETRIN in MTN axon navigation, both in vivo and in vitro. We found no evidence for a role of BMP2/4 or GDF7 in directing MTN axons. However, SLIT-ROBO signaling was found to play a significant role. SLIT proteins are repulsive guidance cues expressed by roof and floor plate. Loss or reduced expression of ROBO2 led to aberrant axon meandering within the dorsal midbrain. Most axons eventually reoriented posteriorly, and only a small fraction crossed the roof plate. Unexpectedly, in the absence of ROBO2, MTN somata migrated into the roof plate, resulting in the loss of a defined roof plate region. Taken together, these results suggest that SLIT2-ROBO2 signaling not only prevents MTN axons from crossing the roof plate but also maintains MTN cell bodies adjacent to the roof plate. With regards to MTN neuron guidance, we conclude that additional roof plate - derived factors are likely to co-operate with SLIT proteins to prevent crossing of the roof plate. Another possibility could be that SLIT might signal through additional receptors.

developmental biology↗

bioRxiv2026

Smad6-mediated inhibition of BMP/TGF-β signaling disrupts midbrain growth in chick embryos

Bone morphogenetic proteins (BMPs) play an important role in dorsal spinal cord patterning. Their presence in the roof plate of the midbrain indicates a role in its development. We examined whether the BMP signaling contributes to dorsal midbrain size expansion in chick embryos by missexpressing pathway activators and inhibitors. Overactivation of BMP4 did not affect midbrain development, whereas GDF7 reduced midbrain growth. In contrast, expression of a truncated dominant-negative BMP receptor type 1b or the extracellular inhibitor Chordin had no detectable effect. Ectopic expression of SMAD6, the intracellular inhibitor of the BMP/ TGF-{beta} pathway, significantly reduced midbrain size, which correlated with decreased proliferation rates of SMAD6-overexpressing cells. In some cases, SMAD6 also disrupted MTN axon trajectory. These results indicate an important role for SMAD-dependent signaling pathways in early dorsal midbrain growth.

developmental biology↗

bioRxiv2025

ISLET-1 knockdown causes abnormal peripheral axonal growth of mesencephalic trigeminal neurones in the chick embryo

The trigeminal is one of the best characterized sensory systems in amniotes. It comprises two populations of first-order sensory neurons: the trigeminal ganglion (TG) which are peripheral to the central nervous system and the mesencephalic trigeminal nucleus (MTN), the only sensory neurons that lie within the central nervous system in amniotes. Islet-1, a LIM homeodomain transcription factor, which plays essential roles during embryogenesis, contributes to axon pathfinding of sensory neurons in the TG. However, if Islet-1 plays a similar role for the MTN neurons is unknown. To answer whether Islet-1 is as important for axon guidance in these centrally - located sensory neurons as it is for the peripherally-located TG neurons, we investigated the effect of reduced Islet-1 expression on axonal pathfinding in the chick MTN. We employed in ovo electroporation to transfect short interfering RNA for Islet-1 (si-Islet-1) into the dorsal midbrain. Our findings showed that, within the central nervous system, Islet-1 knockdown did not affect axonal growth direction of MTN neurons. However, outside the central nervous system a reduction of Islet-1 led to disorganized axonal growth. We observed an abnormal organisation in the maxillary division of the trigeminal nerve when Islet-1 was reduced in MTN neurons.

developmental biology↗

bioRxiv2025

Expression pattern of UNC5H3 during early development of mesencephalon und cerebellum in chicken

The Netrin receptor Uncoordinated-5 receptor C (UNC5C) or UNC5HA has been shown to regulate cell migration in cerebellum and cortex, to control the guidance of the axons in the developing corticospinal tract and to act as a dependence receptor in apoptosis in mouse and rat. We have examined the distribution of UNC5H3 using whole-mount mRNA in situ hybridisation in the embryonic chick, concentrating on its early expression in the mesencephalic/metencephalic region in relation to known ligands, NETRIN1 and NETRIN2. From E2 (embryonic day 2), while the latter are confined to the ventral midline, UNC5H3 is expressed exclusively at the dorsal midline from the diencephalon caudally. Later in development, UNC5H3 is maintained in the rhombic lip (E5 onwards) and subsequently expressed in its putative derivatives; cerebellar granule cells and nuclei within the avian auditory hindbrain complex and the inferior and superior olive.

developmental biology↗

bioRxiv2018

Extracellular Pax6 regulates tangential Cajal-Retzius cell migration

The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct non-cell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 non-cell autonomous activity on the migration of cortical hem- and septum-derived Cajal-Retzius (CR) neurons by live imaging of flat mount developing cerebral cortices. We observed that blocking extracellular Pax6 disrupts tangential CR cell migration patterns. We found a decrease in the distance travelled and changes both in directionality and in the depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances or reduces contact repulsion in medial and lateral regions, respectively. This study demonstrates that secreted Pax6 controls neuronal migration thus acting as a bona fide morphogen at an early stage of cerebral cortex development.\n\nSummary statementCajal-Retzius cell distribution in the embryonic cortex participates in determining the size and positioning of cortical areas. Here, Kaddour et al. establish that the direct non-cell autonomous activity of the Pax6 transcription factor regulates Cajal-Retzius cell migration.

neuroscience↗