Biology subjects

Blommers, M.

Publications and source records attributed to Blommers, M..

3 recordsLinked to original sources

bioRxiv2024

Innervation of cranial muscles requires Mllt11/Af1q/Tcf7c function during trigeminal ganglion development

The development of cranial nerves, including the trigeminal nerve, and the formation of neuromuscular junctions (NMJs) are crucial processes for craniofacial motor function. Mllt11/Af1q/Tcf7c (henceforth Mllt11), a novel type of cytoskeletal-interacting protein, has been implicated in neuronal migration and neuritogenesis during central nervous system development. However, its role in peripheral nerve development and NMJ formation remains poorly understood. This study investigates the function of Mllt11 during trigeminal ganglion development and its impact on motor innervation of the masseter muscle. We report Mllt11 expression in the developing trigeminal ganglia, suggesting a potential role in cranial nerve development. Using a conditional knockout mouse model to delete Mllt11 in Wnt1-expressing neural crest cells, we assessed trigeminal ganglion development and innervation of the masseter muscle in the jaw. Surprisingly, we find that Mllt11 loss does not affect the initial formation of the trigeminal ganglion but disrupts its cellular composition, with a reduction in the ratio of neural crest-derived Sox10+ cells relative to placode-derived Isl1/2+ cells. Furthermore, our study demonstrates that conditional Mllt11 knockout leads to reduction of neurofilament density and NMJs within the masseter muscle, indicating altered trigeminal motor innervation. Our findings show that Mllt11 regulates the cellular composition of the trigeminal ganglion and is essential for proper trigeminal motor innervation in the masseter muscle.

developmental biology↗

bioRxiv2023

Cerebellar granule cell migration and folia development requires Mllt11/Af1q

The organization of neurons into distinct layers, known as lamination, is a common feature of the nervous system. This process, which arises from the direct coupling of neurogenesis and neuronal migration, plays a crucial role in the development of the cerebellum, a structure exhibiting a distinct folding cytoarchitecture with cells arranged in discrete layers. Disruptions to neuronal migration can lead to various neurodevelopmental disorders, highlighting the significance of understanding the molecular regulation of lamination. Here we report a role Mllt11/Af1q/Tcf7c (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q, also known as Mllt11 transcriptional cofactor 7; henceforth referred to Mllt11) in the migration of cerebellar granule cells (GCs). We now show that Mllt11 plays a role in both tangential and radial migration of GCs. Loss of Mllt11 led to an accumulation of GC precursors in the Rhombic Lip region and a reduction in the number of GCs successfully populating developing folia. Consequently, this results in smaller folia and an overall reduction in cerebellar size. Furthermore, analysis of the anchoring centers reveals disruptions in the perinatal folia cytoarchitecture, including alterations in the Bergmann glia fiber orientation and reduced infolding of the Purkinje cell plate. Lastly, we demonstrate that Mllt11 interacts with Non-muscle Myosin IIB (NMIIB) and regulates its expression. We propose the dysregulation of NMIIB underlies altered GC migratory behavior. Taken together, the findings reported herein demonstrate a role for Mllt11 in regulating neuronal migration within the developing cerebellum, which is necessary for its proper neuroanatomical organization.

developmental biology↗

bioRxiv2022

Retinal neuroblast migration and laminar organization requires the cytoskeletal-interacting protein Mllt11

BackgroundThe vertebrate retina is an organized laminar structure comprised of distinct cell types populating three nuclear layers. During development, each retinal cell type follows a stereotypical temporal order of genesis, differentiation, and migration, giving rise to its stratified organization. Once born, the precise positioning of cells along the apico-basal (radial) axis of the retina is critical for subsequent connections to form, relying on orchestrated migratory processes. While these processes are critical for visual function to arise, the regulators of cellular migration and retinal lamination remain largely unexplored. ResultsWe report a role for a microtubule-interacting protein, Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in mammalian retinal cell migration during retinogenesis. We show that Mllt11 loss-of-function in mouse retinal neuroblasts affected the migration of ganglion and amacrine cells into the ganglion cell layer, and led to their ectopic accumulation in the inner plexiform layer. ConclusionsWe demonstrate that Mllt11 plays a critical role in the migration and lamination of neurons in the retina, and its loss impacted formation of the basal-most retinal layers.

developmental biology↗