Biology subjects

Mello, C. V.

Publications and source records attributed to Mello, C. V..

3 recordsLinked to original sources

bioRxiv2021

Resurgent Na+ currents promote ultrafast spiking in projection neurons that drive fine motor control

The underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood. Here we report that projection neurons in the adult zebra finch song nucleus RA display: 1) robust high-frequency firing, 2) ultra-short half-width spike waveforms, 3) superfast Na+ current inactivation kinetics and 4) large resurgent Na+ currents (INaR). These spiking properties closely resemble those of specialized pyramidal neurons in mammalian motor cortex and are well suited for precise temporal coding. They emerge during the critical period for vocal learning in males but not females, coinciding with a complete switch of modulatory Na+ channel subunit expression from Nav{beta}3 to Nav{beta}4. Dynamic clamping and dialysis of Nav{beta}4s C-terminal peptide into juvenile RA neurons provide evidence that this subunit, and its associated INaR, promote neuronal excitability. We propose that Nav{beta}4 underpins INaR that facilitates precise, prolonged, and reliable high-frequency firing in upper motor neurons.

neuroscience↗

bioRxiv2021

False gene and chromosome losses affected by assembly and sequence errors

Many genome assemblies have been found to be incomplete and contain misassemblies. The Vertebrate Genomes Project (VGP) has been producing assemblies with an emphasis on being as complete and error-free as possible, utilizing long reads, long-range scaffolding data, new assembly algorithms, and manual curation. Here we evaluate these new vertebrate genome assemblies relative to the previous references for the same species, including a mammal (platypus), two birds (zebra finch, Annas hummingbird), and a fish (climbing perch). We found that 3 to 11% of genomic sequence was entirely missing in the previous reference assemblies, which included nearly entire GC-rich and repeat-rich microchromosomes with high gene density. Genome-wide, between 25 to 60% of the genes were either completely or partially missing in the previous assemblies, and this was in part due to a bias in GC-rich 5-proximal promoters and 5 exon regions. Our findings reveal novel regulatory landscapes and protein coding sequences that have been greatly underestimated in previous assemblies and are now present in the VGP assemblies.

genomics↗

bioRxiv2021

Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds

Flight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. The avian ephrin-B3 gene lacks an enhancer that drives midline expression, and is missing in Galliformes. The morphology and wiring at brachial levels of the chick spinal cord resemble those of ephrin-B3 null mice. Importantly, dorsal midline decussation, evident in the mutant mouse, is apparent at the chick brachial level, and is prevented by expression of exogenous ephrin-B3 at the roof plate. Our findings support a role for loss of ephrin-B3 function in shaping the avian brachial spinal cord circuitry and facilitating synchronous wing flapping. TeaserWalking vs flying: Deciphering the organization and evolution of the neuronal network that controls wing flapping in birds.

neuroscience↗