Biology subjects

Lallemend, F.

Publications and source records attributed to Lallemend, F..

4 recordsLinked to original sources

bioRxiv2025

Role of CaMKIIa reticular neurons of caudal medulla in control of posture

Terrestrial quadrupeds actively stabilize dorsal-side-up orientation of the body in space due to activity of the postural control system. Supraspinal influences, including those from the reticular formation, play a crucial role in the operation of this system. However, the role of specific molecularly identified populations of reticular neurons in control of posture remains unknown. The aim of the present study was to reveal the role of CaMKIIa reticular neurons (CaMKIIa-RNs) located in the caudal medulla in control of posture. For this purpose, the effects of unilateral chemogenetic activation/inactivation of CaMKII-RNs on different aspects of postural control were studied in mice. It was found that unilateral activation of CaMKIIa-RNs evoked ipsilateral roll tilt of the head and trunk, caused by flexion/adduction of the ipsilateral limbs and extension/abduction of the contralateral limbs. The body roll tilt was actively stabilized on the tilting platform and maintained during walking. Unilateral inactivation of CaMKIIa-RNs evoked the opposite effects. Histological analyses showed that the population of CaMKIIa-RNs in the caudal medulla contains reticulospinal neurons that project to the spinal cord mainly through ipsilateral lateral funiculus and terminate in the intermediate area of the gray matter. We demonstrated that although the population of CaMKIIa-RNs contains both excitatory and inhibitory neurons, the excitatory ones dominate. Thus, CaMKIIa-RNs located in the caudal medulla play a crucial role for maintenance of the dorsal-side-up body orientation in different environments. Left/right symmetry and asymmetry in activity of CaMKIIa-RNs allows animals to maintain dorsal-side-up body orientation on horizontal and laterally inclined surfaces, respectively.

neuroscience↗

bioRxiv2024

Posterior specification of multi-lineage axial assembloids from human pluripotent stem cells.

Elongation of the posterior body axis is driven by multi-potent neuromesodermal progenitors (NMPs), which both self-renew and simultaneously generate neural tube, neural crest, and presomitc mesoderm lineages at successive anterior posterior (A-P) levels. The ensuing diversification of these three NMP lineages is remarkably extensive, and also essential for an immense range of clinically important adult posterior body tissues. Here, we describe a human pluripotent stem cell protocol that successfully specifies authentic NMPs using a cocktail of seven factors (7F). 7F-NMPs express requisite markers, exhibit co-linear HOX activation, and can be purposely specified into each of the three NMP daughter lineages, demonstrating genuine multi-potency. 3D assembly of neural tube, neural crest, and presomitic mesoderm spheroids followed by long-term floating culture derives mature, multi-compartment Posterior Axial Assembloids, or PAXAs. PAXAs constitute a complex heterogeneous tissue containing spinal motor neurons and interneurons, central and peripheral glia, connective tissues, muscle satellite cells and contractile muscle fibres. Together, 7F-NMP and PAXA protocols establish a versatile in vitro platform to model mechanisms of human posterior body axis development, and for the study of a wide range of human diseases.

cell biology↗

bioRxiv2023

Motor nerves direct the development of the sympathetic nervous system

The sympathetic nervous system controls a wide spectrum of bodily functions including operation of vessels, cardiac rhythm, and the "flight or fight response". Sympathetic neurons, which are neural crest-derived, develop in coordination with presynaptic motor nerves extending from the central nervous system (CNS). By using nerve-selective genetic ablations, we revealed that sympathetic ganglia development depends on CNS-derived motor innervation. In the absence of preganglionic motor nerves, trunk sympathetic chain ganglia were fragmented and smaller in size, while cervical ganglia were severely misshapen. Sympathetic neurons were misplaced along sensory fibers and projected towards abnormal paths, in some cases invading the sensory dorsal root ganglia. The misplaced progenitors of sympathoblasts corresponded to the nerve-associated, neural crest-derived Schwann cell precursors (SCPs). Notably, we found that SCPs activate the autonomic marker PHOX2B while migrating along motor nerves towards the region of the dorsal aorta in wildtype embryos, suggesting that SCP differentiate into sympathetic neurons while still nerve-associated in motor-ablated embryos. Ligand-receptor prediction from single cell transcriptomic data coupled with functional studies identified Semaphorin 3A/3F as candidate motor nerve-derived signals influencing neural crest migration along axons. Thus, motor nerves control the placement of sympathoblasts and their subsequent axonal navigation during critical periods of sympathetic chain development.

developmental biology↗

bioRxiv2021

Theory of branching morphogenesis by local interactions and global guidance

Branching morphogenesis governs the formation of many organs such as lung, kidney, and the neurovascular system. Many studies have explored system-specific molecular and cellular regulatory mechanisms, as well as self-organizing rules underlying branching morphogenesis. However, in addition to local cues, branched tissue growth can also be influenced by global guidance. Here, we develop a theoretical framework for a stochastic self-organized branching process in the presence of external cues. Combining analytical theory with numerical simulations, we predict differential signatures of global vs. local regulatory mechanisms on the branching pattern, such as angle distributions, domain size, and space-filling efficiency. We find that branch alignment follows a generic scaling law determined by the strength of global guidance, while local interactions influence the tissue density but not its overall territory. Finally, using zebrafish innervation as a model system, we test these key features of the model experimentally. Our work thus provides quantitative predictions to disentangle the role of different types of cues in shaping branched structures across scales.

biophysics↗