Motor Innervation Research Articles

Involvement of catecholaminergic neurons in motor innervation of striated muscle in the mouse esophagus.

Enteric co-innervation is a peculiar innervation pattern of striated esophageal musculature. Both anatomical and functional data on enteric co-innervation related to various transmitters have been collected in different species, although its function remains enigmatic. However, it is unclear whether catecholaminergic components are involved in such a co-innervation. Thus, we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus, using immunohistochemistry with antibodies against tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT) and protein gene product 9.5 (PGP 9.5), α-bungarotoxin (α-BT) and PCR with primers for amplification of cDNA encoding TH and dopamine-β-hydroxylase (DBH). TH-positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14% of α-BT-labelled motor endplates differing from VAChT-positive vagal nerve terminals. TH-positive perikarya represented a subpopulation of only about 2.8% of all PGP 9.5-positive myenteric neurons. Analysis of mRNA showed both TH and DBH transcripts in the mouse esophagus. As ChAT-positive neurons in the compact formation of the nucleus ambiguus were negative for TH, the TH-positive nerve varicosities on motor endplates are presumably of enteric origin, although a sympathetic origin cannot be excluded. In the medulla oblongata, the cholinergic ambiguus neurons were densely supplied with TH-positive varicosities. Thus, catecholamines may modulate vagal motor innervation of esophageal-striated muscles not only at the peripheral level via enteric co-innervation but also at the central level via projections to the nucleus ambiguus. As Parkinson's disease, with a loss of central dopaminergic neurons, also affects the enteric nervous system and dysphagia is prevalent in patients with this disease, investigation of intrinsic catecholamines in the esophagus may be worthwhile to understand such a symptom.

How to avoid from an ectropion complication by using motor innervation prevention at lower eyelid blepharoplasty surgery

The subciliary incision is the most commonly used approach for lower eyelid blepharoplasty because of the advantages like ease of combining with other periocular and midface rejuvenation techniques. However, the most common reported major complication is lower lid malposition. In this article we described our subciliary dissection technique to protect the motor branches of tarsal orbicularis oculi to avoid from ectropion.

Anatomical study of the motor branches of the median nerve to the forearm and guidelines for selective neurectomy.

The median nerve is responsible for the motor innervation of most of the muscles usually involved in upper limb spasticity. Selective neurectomy is one of the treatments utilized to reduce spasticity. The purpose of this study was to describe the variations of the motor branches of the median nerve in the forearm and draw recommendations for an appropriate planning of selective neurectomy. The median nerve was dissected in the forearm of 20 fresh cadaver upper limbs. Measurements included number, origin, division, and entry point of each motor branch into the muscles. One branch for the pronator teres was the most common pattern. In 9/20 cases, it arose as a common trunk with other branches. A single trunk innervated the flexor carpi radialis with a common origin with other branches in 17/20 cases. Two, three or four branches innervated the flexor digitorum superficialis, the first one frequently through a common trunk with other branches. They were very difficult to identify unless insertions of pronator teres and flexor digitorum superficialis were detached. The flexor digitorum profundus received one to five branches and flexor pollicis longus one to two branches from the anterior interosseous nerve. There is no regular pattern of the motor branches of the median nerve in the forearm. Our findings differ in many points from the classical literature. Because of the frequency of common trunks for different muscles, we recommend the use of peroperative electrical stimulation. Selective neurotomy of flexor digitorum superficialis is technically difficult, because the entry point of some of their terminal branches occurs just below the arch and deep to the muscle belly.

Evidence for a trigeminal mesencephalic-hypoglossal nuclei loop involved in controlling vibrissae movements in the rat.

Previous studies performed in rats showed that the whisker-pad motor innervation involves not only the facial nerve, but also some hypoglossal neurons whose axons travel within the trigeminal infraorbital nerve (ION) and target the extrinsic muscles surrounding the whisker-pad macrovibrissae. Furthermore, the electrical stimulation of the ION induced an increase in the EMG activity of these muscles, while the hypoglossal nucleus stimulation elicited evoked potentials and single motor unit responses. However, the existence of a neural network able to involve the XIIth nucleus in macrovibrissae whisking control was totally unknown until now. Since other recent experiments demonstrated that: (1) the mesencephalic trigeminal nucleus (Me5) neurons respond to both spontaneous and artificial movements of macrovibrissae, and (2) the Me5 peripheral terminals provide a monosynaptic sensory innervation to the macrovibrissae, the present study was aimed at analyzing a possible role of the Me5 nucleus as a relay station in the sensory-motor loop that involves the XIIth nucleus neurons in rhythmic whisking control. Two tracers were used in the same animal: Fluoro Gold, which was injected into the whisker pad to retrogradely label the hypoglossal whisker-pad projection neurons, and Dil, which was instead injected into the Me5 to label its projections to these hypoglossal neurons. Results demonstrated that terminals of the Me5 neurons monosynaptically target the hypoglossal whisker-pad projection neurons. The functional role of this sensory-motor connection is discussed, with particular regard to a hypothesized proprioceptive reflex in whisker-pad extrinsic muscles that can be elicited by the activation of the Me5 macrovibrissae receptors.

Neuroanatomical characteristics of deep and superficial needling using LI11 as an example.

ObjectivesTo compare the neuroanatomical characteristics of the deep and superficial tissues at acupuncture point LI11 using a neural tracing technique, in order to examine the neural basis of potential differences between deep and superficial needling techniques.MethodsIn order to mimic the situations of the deep and superficial needling, the retrograde neural tracer Alexa Fluor 488 conjugate of cholera toxin subunit B (AF488-CTB) was injected into the muscle or subcutaneous tissue, respectively, at acupuncture point LI11 in eight rats (n=4 each). Three days following injection, the distribution of motor and sensory neurons labelled with AF488-CTB was examined in the spinal cord and dorsal root ganglia (DRG) under a fluorescent microscope.ResultsFor both types of injection, labelled motor and sensory neurons were distributed on the side ipsilateral to the injection in the spinal cord and DRG between spinal levels C5 and T1. The number of labelled motor neurons following intramuscular injection was significantly higher than subcutaneous injection. By contrast, the number of labelled sensory neurons following subcutaneous injection was significantly higher in number and extended over a greater number of spinal segments compared to intramuscular injection.ConclusionsThese data indicate that the motor and sensory innervation of muscle and subcutaneous tissue beneath LI11 differ, and suggest that acupuncture signals induced by deep and superficial needling stimulation may be transmitted through different neural pathways.

SPARC triggers a cell-autonomous program of synapse elimination

Elimination of the excess synaptic contacts established in the early stages of neuronal development is required to refine the function of neuronal circuits. Here we investigate whether secreted protein acidic and rich in cysteine (SPARC), a molecule produced by glial cells, is involved in synapse removal. SPARC production peaks when innervation of the rat superior cervical ganglion and the tail of Xenopus tropicalis tadpoles are remodeled. The formation of new cholinergic synapses in autaptic single-cell microcultures is inhibited by SPARC. The effect resides in the C-terminal domain, which is also responsible for triggering a concentration- and time-dependent disassembly of stable cholinergic synapses. The loss of synaptic contacts is associated with the formation of retracted axon terminals containing multivesicular bodies and secondary lysosomes. The biological relevance of in vitro results was supported by injecting the tail of Xenopus tropicalis tadpoles with peptide 4.2, a 20-aa sequence derived from SPARC that mimics full-length protein effects. Swimming was severely impaired at ∼5 h after peptide application, caused by the massive elimination of neuromuscular junctions and pruning of axonal branches. Effects revert by 6 d after injection, as motor innervation reforms. In conclusion, SPARC triggers a cell-autonomous program of synapse elimination in cholinergic neurons that likely occurs when protein production peaks during normal development.

Ultrasound of the Hypoglossal Nerve in the Neck: Visualization and Initial Clinical Experience with Patients.

The hypoglossal nerve, providing motor innervation for the tongue, can be affected in many diseases of the neck and skull base, leading to dysarthria, dysphagia, and ultimately atrophy of the tongue. We determined the feasibility of direct visualization of the hypoglossal nerve in the neck with ultrasound, testing this technique on healthy volunteers and evaluating it in clinical practice. The study consisted of 4 parts: first, ultrasound-guided perineural ink injections along the course of the hypoglossal nerve at 24 sides of 12 fresh, nonembalmed cadaver necks. Subsequently, the specimens were dissected to confirm the correct identification of the nerve. The second part was examination of healthy volunteers with ultrasound and measurement of cross-sectional areas for generating reference data. The third part was scanning of healthy volunteers by 2 resident physicians with little and intermediate experience in ultrasound. Fourth was examination with ultrasound of patients with motor symptoms of the tongue. The hypoglossal nerve was correctly identified bilaterally in all cadaveric specimens (24/24) and all volunteers (33/33). The cross-sectional area ranged from 1.9 to 2.1 mm(2). The resident physicians were able to locate the nerve in 19 of 22 cases, demonstrating that locating the nerve is reproducible and feasible even with intermediate experience in ultrasound. Finally, alterations of the hypoglossal nerve in disease states could be depicted. Direct, reliable, and reproducible visualization of the extracranial hypoglossal nerve with ultrasound is feasible.

Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part I.

The vagus nerve (VN), the "great wondering protector" of the body, comprises an intricate neuro-endocrine-immune network that maintains homeostasis. With reciprocal neural connections to multiple brain regions, the VN serves as a control center that integrates interoceptive information and responds with appropriate adaptive modulatory feedbacks. While most VN fibers are unmyelinated C-fibers from the visceral organs, myelinated A- and B-fiber play an important role in somatic sensory, motor, and parasympathetic innervation. VN fibers are primarily cholinergic but other noncholinergic nonadrenergic neurotransmitters are also involved. VN has four vagal nuclei that provide critical controls to the cardiovascular, respiratory, and alimentary systems. Latest studies revealed that VN is also involved in inflammation, mood, and pain regulation, all of which can be potentially modulated by vagus nerve stimulation (VNS). With a broad vagal neural network, VNS may exert a neuromodulatory effect to activate certain innate "protective" pathways for restoring health.

Transmembrane proteoglycans syndecan-2, 4, receptor candidates for the impact of HGF and FGF2 on semaphorin 3A expression in early-differentiated myoblasts.

Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed an unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2) triggered its expression exclusively at the early differentiation phase. In order to advance this concept, the present study described that transmembrane heparan/chondroitin sulfate proteoglycans syndecan-2, 4 may be the plausible receptor candidates for HGF and FGF2 to signal Sema3A expression. Results showed that mRNA expression of syndecan-2, 4 was abundant (two magnitudes higher than syndecan-1, 3) in early-differentiated myoblasts and their in vitro knockdown diminished the HGF/FGF2-induced expression of Sema3A down to a baseline level. Pretreatment with heparitinase and chondroitinase ABC decreased the HGF and FGF2 responses, respectively, in non–knockdown cultures, supporting a possible model that HGF and FGF2 may bind to heparan and chondroitin sulfate chains of syndecan-2, 4 to signal Sema3A expression. The findings, therefore, extend our understanding that HGF/FGF2-syndecan-2, 4 association may stimulate a burst of Sema3A secretion by myoblasts recruited to the site of muscle injury; this would ensure a coordinated delay in the attachment of motoneuron terminals onto fibers early in muscle regeneration, and thus synchronize the recovery of muscle fiber integrity and the early resolution of inflammation after injury with reinnervation toward functional recovery.

Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions.

Skeletal muscle maintenance depends on motor innervation at neuromuscular junctions (NMJs). Multiple mechanisms contribute to NMJ repair and maintenance; however muscle stem cells (satellite cells, SCs), are deemed to have little impact on these processes. Therefore, the applicability of SC studies to attenuate muscle loss due to NMJ deterioration as observed in neuromuscular diseases and aging is ambiguous. We employed mice with an inducible Cre, and conditionally expressed DTA to deplete or GFP to track SCs. We found SC depletion exacerbated muscle atrophy and type transitions connected to neuromuscular disruption. Also, elevated fibrosis and further declines in force generation were specific to SC depletion and neuromuscular disruption. Fate analysis revealed SC activity near regenerating NMJs. Moreover, SC depletion aggravated deficits in reinnervation and post-synaptic morphology at regenerating NMJs. Therefore, our results propose a mechanism whereby further NMJ and skeletal muscle decline ensues upon SC depletion and neuromuscular disruption.

L’innervation motrice de la face. Anatomie chirurgicale et radiologique des paralysies faciales et de leur réparation chirurgicale

Motor innervation of the face depends on the facial nerve for the mobility of the face, on the mandibular nerve, third branch of the trigeminal nerve, which gives the motor innervation of the masticator muscles, and the hypoglossal nerve for the tongue. In case of facial paralysis, the most common palliative surgical techniques are the lengthening temporalis myoplasty (the temporal is innervated by the mandibular nerve) and the hypoglossal-facial anastomosis. The aim of this work is to describe the surgical anatomy of these three nerves and the radiologic anatomy of the facial nerve inside the temporal bone. Then the facial nerve penetrates inside the parotid gland giving a plexus. Four branches of the facial nerve leave the parotid gland: they are called temporal, zygomatic, buccal and marginal which give innervation to the cutaneous muscles of the face. Mandibular nerve gives three branches to the temporal muscles: the anterior, intermediate and posterior deep temporal nerves which penetrate inside the deep aspect of the temporal muscle in front of the infratemporal line. The hypoglossal nerve is only the motor nerve to the tongue. The ansa cervicalis, which is coming from the superficial cervical plexus and joins the hypoglossal nerve in the submandibular area is giving the motor innervation to subhyoid muscles and to the geniohyoid muscle.

Why the heart is like an orchestra and the uterus is like a soccer crowd

The human uterus has no pacemaker or motor innervation, yet develops rhythmic, powerful contractions that increase intrauterine pressure to dilate the cervix and force the fetus through the pelvis. To achieve the synchronous contractions required for labor, the muscle cells of the uterus act as independent oscillators that become increasingly coupled by gap junctions toward the end of pregnancy. The oscillations are facilitated by changes in resting membrane potential that occur as pregnancy progresses. Reductions of potassium channels in the myocyte membranes in late pregnancy prolong myocyte action potentials, further facilitating transmission of signals and recruitment of neighboring myocytes. Late in pregnancy prostaglandin production increases leading to increased myocyte excitability. Also late in pregnancy myocyte actin polymerizes allowing actin-myosin interactions that generate force, following myocyte depolarization, calcium entry, and activation of myosin kinase. Labor occurs as a consequence of the combination of increased myocyte to myocyte connectivity, increased depolarizations that last longer, and activated intracellular contractile machinery. During labor the synchronous contractions of muscle cells raise intrauterine pressure to dilate the cervix in a process distinct from peristalsis. The synchronous contractions occur in a progressively larger region of the uterine wall. As the size of the region increases with increasing connectivity, the contraction of that larger area leads to an increase in intrauterine pressure. The resulting increased wall tension causes myocyte depolarization in other parts of the uterus, generating widespread synchronous activity and increased force as more linked regions are recruited into the contraction. The emergent behavior of the uterus has parallels in the behavior of crowds at soccer matches that sing together without a conductor. This contrasts with the behavior of the heart where sequential contractions are regulated by a pacemaker in a similar way to the actions of a conductor and an orchestra.

The innervation of the muscle spindle: a personal history.

I present a brief review of current understanding of the innervation of the mammalian muscle spindle, from a personal historical perspective. The review begins with comparative studies on the numbers of spindle afferents and considers how their relative abundance may best be assessed. This is followed by an examination of the distribution and some functional properties of the motor innervation. The primary ending is the subject of the final section, in particular, I look at what can be learned from serial sectioning and volumetric reconstruction, and present new results on a model and simulations concerning sensory terminal deformation during stretch.

Experiences with functional gracilis muscle flap in lower lip reconstruction.

Reconstruction of the lips is pivotal because the lips play an essential role in facial aesthetics and have unique functional properties. We presented our experience in reconstruction of total or subtotal lower lip defects with functional gracillis muscle flap covered split-thickness skin graft (STSG) in patients. Between 2009 and 2011, seven patients underwent resection of lower lip squamous cell carcinoma and lip reconstruction. Gracillis muscle flap was performed for reconstruction. Recipient vessels were the facial artery and vein. Motor nerve of the gracillis muscle was coapted to the marginal branch of the facial nerve. Gracillis muscle was covered with STSG. Patients were evaluated about mouth opening, oral competence, word articulation, the color match of the graft, the contraction of the muscle by physical examination. Electromyographic studies and sensation tests were performed. Postoperative course was uneventful for all of the flaps. No microvascular revisions were needed. One patient was reoperated because of wound dehiscence under local anaesthesia. Mean follow up period was 15 months. After three months, movement of the reconstructed lip was observed. Color of the grafted skin was matched with the skin of the face. The patients had no problems with word articulation, oral continence, or mouth opening. The electromyographic study showed recovery of motor innervation. After 1 year, the patients demonstrated recovered sensitivity with the sensation test. Considering functional results, superior aesthetic appearance, and minimal donor-site morbidity of the functional gracillis transfer covered skin graft, we think that this method may be an alternative for reconstruction of large full-thickness defects of the lower lip. © 2015 Wiley Periodicals, Inc. Microsurgery 37:487-493, 2017.

Interspecies Differences in Electromechanical and Histological Characteristics of Human and Swine Esophagus1

Interspecies Differences in Electromechanical and Histological Characteristics of Human and Swine Esophagus1

The innervation of the zebrafish pharyngeal jaws and teeth.

Zebrafish (Danio rerio) teeth are increasingly used as a model to study odontogenesis in non-mammalians. Using serial semi-thin section histology and immunohistochemistry, the nerves innervating the pharyngeal jaws and teeth have been identified. The last pair of branchial arches, which are non-gill bearing but which carry the teeth, are innervated by an internal branch of a post-trematic ramus of the vagal nerve. Another, external, branch is probably responsible for the motor innervation of the branchiomeric musculature. Nerve fibres appear in the pulp cavity of the teeth only late during cytodifferentiation, and are therefore likely not involved in early steps of tooth formation. The precise role of the nervous system during continuous tooth replacement remains to be determined. Nonetheless, this study provides the necessary morphological background information to address this question.

399. Early Correction of Neuromuscular Deficits in Pompe Disease Is Required for Restoration of Strength Following Gene Therapy

We have recently reported pathology of the neuromuscular junction (NMJ) in Pompe disease, reflecting disruption of neuronal and muscle homeostasis as a result of glycogen accumulation. The objective of this study was to examine how alterations of the NMJ contribute to Pompe disease pathology. An AAV9 vector encoding GAA (AAV9-hGAA) was injected directly into the tibialis anterior muscle of Gaa-/- mice at early- mid- and severe- pathological time points. Gene expression of NMJ-related genes, in situ muscle force production, clearance of glycogen in conjunction with histological assessment of the NMJ was subsequently performed in all animals. Our data demonstrate that AAV9-hGAA is able to replace GAA to the affected tissue and modify AChR mRNA expression, muscle force production, motor endplate expansion and innervation status of the NMJ. The degree of restoration for these outcomes is limited by progression of neural pathology. Early restoration of GAA activity in muscle and neural cells was most effective, while late correction of GAA expression was not effective in modifying parameters reflecting NMJ structure and function nor in force restoration despite resolution of glycogen storage in muscle. Our data provide new mechanistic insight into the pathology of Pompe disease and suggest that early systemic correction to both neuronal and muscle tissues may be essential for successful correction of neuromuscular function in Pompe disease.

Cauda Equina Syndrome (CES) Secondary to Lumbar Disc Herniation: Retrospective Clinical Study in 13 Cases with in Progression Symptoms

Introduction A compression of nerve roots of cauda equina (CE) is responsible for cauda equina syndrome (CES). The nine pairs of CE nerve roots provide motor and sensory innervation to the lower extremity muscles, the pelvic floor, and the bowel and bladder sphincters. CES caused by a massive herniated lumbar disc, has rarely been described in literature. We report 13 cases of massive lumbar disc herniation causing CES which underwent surgical intervention after 48 hours or more from the trauma. Material and Methods Between September 2010 and June 2014, 13 cases of CES by lumbar disc herniation were treated in our department. In eight patients the herniated disc level was L4–L5, in one patient was L3–L4, and in four cases was L5–S1. The patients admitted to our hospital had lumbosciatic pain and worsening progressive: motor weakness (seven cases), hypoesthesia to lower limbs (nine cases), sexual dysfunction (two cases), hypo/areflexia (five cases). All the patients before surgery referred sphincter disorders (SD). The surgery was performed in a range from 48 hours to 8 days by the onset of symptomatology. Magnetic resonance imaging (MRI) of the lumbosacral region was performed in all cases before surgery; other postsurgical studies include electromyography (EMG), urodynamic study, RigiScan, and GSA. Results The MRI examinations showed a herniated lumbar disc determining a compression on CE. Of 13 patients, 11 had a complete recovery of sphincter disturbances and 8 had a recovery of neurological symptoms in the first day after surgery. Eight patients were discharged in the 3rd day after surgery and had a complete clinical recovery after 1 month from surgery. Conclusion CES is characterized by the following symptoms: low back pain, saddle anesthesia, hypo/areflexia, motor weakness or sensory disturbances to lower limbs, sphincter disorders, and sexual disorders. We classified CES according to the onset of symptoms in an acute (symptoms occur within 24 hours) and an in progression form (more than 24 hours). According to the clinical features CES can be classified in a complete (sphincter disorders plus at least four other criteria) and an incomplete form (sphincter disorders and three or less symptoms). Our study is aimed to elaborate a score to better define the preoperative symptomatology and give a prognostic evaluation about neurological recovery. In our experience, despite the fact that surgery has been performed at least 48 hours after the symptoms occurred, we had a complete neurological recovery in 10 out of 13 cases. In case of in progression CES, the surgical intervention, even if it is not performed within 12 hours, can allow a complete neurological recovery, depending on the severity of the clinical features at the time of surgery.

PP02.5 – 2943: Neurological outcome in MMC patients after fetal surgery – Results from the Zurich cohort

Objective The purpose of this study was to investigate the neurological outcome of patients with meningomyelocele treated with fetal closure in Zurich. Methods 14 patients were included, of two data were collected retrospectively, 12 were followed prospectively by a detailed evaluation protocol. We investigated the anatomical spinal level in utero before surgery by in utero MR imaging. The functional spinal level at birth, 3 months, 6 months and 12 months of age was compared to the anatomical level in utero. Chiari II-malformation and remission of hindbrain herniation over the course was investigated by MRI. Data of head circumference, shunt placement, bladder dysfunction and development were collected. Our results were compared to the results of the MOMS study (A randomized trial of prenatal versus postnatal repair of myelomeningocele. Adzick et al. NEJM, 2011 Mar 17;364(11):993–1004). Results Anatomical level in utero ranged between L1 to L5. According to the anatomical level the functional level after surgery was two or more levels better in 28%, level of function one level better in 21%, no difference was seen in 43%, level of function two level worse in 7%. Interestingly 75% of our patients had partial motor innervation below the functional level. Before surgery Chiari II-malformation was detected in all 14 patients, after fetal surgery we had no evidence of hindbrain herniation in any. In 46.1% shunt placement was necessary. 66% had neurogenic bladder dysfunction. Conclusion Our results from this small cohort show nearly the same results as reported in the MOMS trial, especially regarding shunt placement. A part of our patients showed a relevant partial motor innervation below the level, it is to discuss if this could be a result of fetal intervention, just as the low frequency of shunt placement and complete demission of hindbrain herniation.

Nkx2.2 and Nkx2.9 are the key regulators to determine cell fate of branchial and visceral motor neurons in caudal hindbrain.

Cranial motor nerves in vertebrates are comprised of the three principal subtypes of branchial, visceral, and somatic motor neurons, which develop in typical patterns along the anteroposterior and dorsoventral axes of hindbrain. Here we demonstrate that the formation of branchial and visceral motor neurons critically depends on the transcription factors Nkx2.2 and Nkx2.9, which together determine the cell fate of neuronal progenitor cells. Disruption of both genes in mouse embryos results in complete loss of the vagal and spinal accessory motor nerves, and partial loss of the facial and glossopharyngeal motor nerves, while the purely somatic hypoglossal and abducens motor nerves are not diminished. Cell lineage analysis in a genetically marked mouse line reveals that alterations of cranial nerves in Nkx2.2; Nkx2.9 double-deficient mouse embryos result from changes of cell fate in neuronal progenitor cells. As a consequence progenitors of branchiovisceral motor neurons in the ventral p3 domain of hindbrain are transformed to somatic motor neurons, which use ventral exit points to send axon trajectories to their targets. Cell fate transformation is limited to the caudal hindbrain, as the trigeminal nerve is not affected in double-mutant embryos suggesting that Nkx2.2 and Nkx2.9 proteins play no role in the development of branchiovisceral motor neurons in hindbrain rostral to rhombomere 4.