<i>In vivo</i>
            expansion of functionally integrated
            <scp>GABA</scp>
            ergic interneurons by targeted increase in neural progenitors

Shaw, Rachel E; Kottler, Benjamin; Ludlow, Zoe N.; Buhl, Edgar; Kim, Dong-Wook; Silva, Sara Morais da; Miedzik, A. A.; Coum, Antoine; Hodge, James J L; Hirth, Frank; Sousa‐Nunes, Rita

doi:10.15252/embj.201798163

Cited by 20 publications

(28 citation statements)

References 63 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To identify the adult brain structures and associated functional modalities that derive from the embryonic DTB, we utilized genetic tracing of neural lineages employing the tracer line UAS-mCD8::GFP, tub-FRT-CD2-FRT-Gal4, UAS-FLP/CyO GMR Dfd YFP (39,40). We first deployed en-Gal4 as driver, which, combined with the tracer line, causes permanent GFP labeling of progeny of engrailed-expressing cells, even when those progeny themselves no longer express engrailed.…”

Section: Resultsmentioning

confidence: 99%

Ancestral regulatory mechanisms specify conserved midbrain circuitry in arthropods and vertebrates

Bridi

Ludlow

Kottler

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Corresponding attributes of neural development and function suggest arthropod and vertebrate brains may have an evolutionarily conserved organization. However, the underlying mechanisms have remained elusive. Here, we identify a gene regulatory and character identity network defining the deutocerebral–tritocerebral boundary (DTB) in Drosophila. This network comprises genes homologous to those directing midbrain-hindbrain boundary (MHB) formation in vertebrates and their closest chordate relatives. Genetic tracing reveals that the embryonic DTB gives rise to adult midbrain circuits that in flies control auditory and vestibular information processing and motor coordination, as do MHB-derived circuits in vertebrates. DTB-specific gene expression and function are directed by cis-regulatory elements of developmental control genes that include homologs of mammalian Zinc finger of the cerebellum and Purkinje cell protein 4. Drosophila DTB-specific cis-regulatory elements correspond to regulatory sequences of human ENGRAILED-2, PAX-2, and DACHSHUND-1 that direct MHB-specific expression in the embryonic mouse brain. We show that cis-regulatory elements and the gene networks they regulate direct the formation and function of midbrain circuits for balance and motor coordination in insects and mammals. Regulatory mechanisms mediating the genetic specification of cephalic neural circuits in arthropods correspond to those in chordates, thereby implying their origin before the divergence of deuterostomes and ecdysozoans.

show abstract

Section: Resultsmentioning

confidence: 99%

Ancestral regulatory mechanisms specify conserved midbrain circuitry in arthropods and vertebrates

Bridi

Ludlow

Kottler

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…To identify the adult brain structures and functional modalities that arise from the embryonic DTB, we used genetic tracing of neural lineages (38,39). We traced engrailed expressing lineages of the embryonic neuroectodermal DTB (SI Appendix Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Mechanical stimuli trains consisted of 5 pulses of 200ms each, spaced by 800ms. Motor behaviour parameters were determined as previously described (38,75,76).…”

Section: In Situ Hybridization Immunocytochemistry and Imagementioning

confidence: 99%

Ancestral Regulatory Mechanisms Specify Conserved Midbrain Circuitry in Arthropods and Vertebrates

Bridi

Ludlow

Kottler

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Corresponding attributes of neural development and function suggest arthropod and vertebrate brains may have an evolutionarily conserved organization. However, the underlying mechanisms have remained elusive. Here we identify a gene regulatory and character identity network defining the deutocerebral-tritocerebral boundary (DTB) in Drosophila. We show this network comprises genes homologous to those directing midbrain-hindbrain boundary (MHB) formation in vertebrates and their closest chordate relatives. Genetic tracing reveals that the embryonic DTB gives rise to adult midbrain circuits that in flies control auditory and vestibular information processing and motor coordination, as do MHB-derived circuits in vertebrates. DTB-specific gene expression and function is directed by cis-regulatory elements (CREs) of developmental control genes that include homologs of mammalian Zinc finger of the cerebellum and Purkinje cell protein 4. Moreover, Drosophila DTBspecific CREs correspond to regulatory sequences of human ENGRAILED-2, PAX-2 and DACHSHUND-1 that direct MHBspecific expression in the embryonic mouse brain. Together, these findings imply ancestral regulatory mechanisms mediating the genetic specification of midbrain-cerebellar circuitry for balance and motor control that may predated the radiation of cephalic nervous systems across the animal kingdom.

show abstract

“…But very few attempts have been there to link the two aspects (Tejedor et al , ; de Belle and Heisenberg, ; Walcourt and Nash, ; Hong et al , ; Blumröder et al , ). Shaw et al () have studied the effect of induced increase in progenitors and neuronal numbers in EB by attenuation of Prospero function. They have shown that the supernumerary neurons could form functional connections and could generate normal physiological and motor responses.…”

Section: Discussionmentioning

confidence: 99%

Developmental Deformity Due to scalloped Non‐Function in Drosophila Brain Leads to Cognitive Impairment

Rohith

Shyamala

2019

Developmental Neurobiology

View full text Add to dashboard Cite

Neural identity and wiring specificity are fundamental to brain function. Factors affecting proliferation of the progenitor cells leading to an expansion or regression of specific neuronal clusters are expected to challenge the process of formation of precise synaptic connections with their partners and their further integration to result in proper functional neural circuitry. We have investigated the role of scalloped, a Hippo pathway gene in Drosophila brain development and have shown that its function is critical to regulate proliferation of Mushroom Body Neuroblasts and to limit the neuronal cluster size to normal in the fly brain. Here we investigate the consequent effect of the anatomical phenotype of mutant flies on the brain function, as exemplified by their cognitive performance. We demonstrate that the neural expansion in important neural clusters of the olfactory pathway, caused due to Scalloped inactivation, imparts severe disabilities in learning, short-term memory and long-term memory. Scalloped knockdown in αβ Kenyon Cell clusters drastically reduces long-term memory performance. Scalloped deficiency induced neural expansion in antennal lobe and ellipsoid body neurons bring down short-term memory performance significantly. We also demonstrate that the cognitive impairments observed here are not due to a problem in memory formation or execution in the adult, but are due to the developmental deformities caused in the respective class of neurons. Our results strongly indicate that the additional neurons generated by Scalloped inactivation are not synergistically integrated into, but rather perturb the formation of precise functional circuitry.

show abstract

In vivo expansion of functionally integrated GABA ergic interneurons by targeted increase in neural progenitors

Cited by 20 publications

References 63 publications

Ancestral regulatory mechanisms specify conserved midbrain circuitry in arthropods and vertebrates

Ancestral regulatory mechanisms specify conserved midbrain circuitry in arthropods and vertebrates

Ancestral Regulatory Mechanisms Specify Conserved Midbrain Circuitry in Arthropods and Vertebrates

Developmental Deformity Due to scalloped Non‐Function in Drosophila Brain Leads to Cognitive Impairment

Contact Info

Product

Resources

About