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Biology subjects

Black, M. E.

Publications and source records attributed to Black, M. E..

2 recordsLinked to original sources

Biomechanical simplification of the motor control of whisking

1.Animal nervous systems must coordinate the sequence and timing of numerous muscles - a challenging control problem. The challenge is particularly acute for highly mobile sensing structures with many degrees of freedom, such as eyes, pinnae, hands, forepaws, and whiskers, because these low-mass, distal sensors require complex muscle coordination. This work examines how the geometry of the rat whisker array simplifies coordination required for "whisking" behavior 1-3. During whisking, 33 intrinsic ("sling") muscles are the primary drivers 4-12 of the rapid, rhythmic protractions of the large mystacial vibrissae (whiskers), which vary more than sixfold in length and threefold in base diameter 13-16. Although whisking is a rhythmic, centrally-patterned behavior 17-24, rodents can change the position, shape, and size of the whisker array, indicating considerable voluntary control 25-34. To begin quantifying how the arrays biomechanics contribute to whisking movements, we used three-dimensional anatomical reconstructions of follicle and sling muscle geometry to simulate the movement resulting from a "uniform motor command," defined as equal firing rates across all sling muscle motor neurons. This simulation provides a baseline profile of protraction under anatomically realistic but uniformly driven conditions. It does not isolate neural from biomechanical contributions but helps identify deviations that suggest active control. Simulations reveal that all follicles rotate through approximately equal angles, regardless of size. The angular fanning of the whiskers at their bases increases monotonically throughout protraction, while maximum distance between whisker tips occurs at approximately 90% of resting muscle length, after which whisker tips converge and sensing resolution increases monotonically.

neuroscience↗

Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation

The organization of the genome in three-dimensional space is highly dynamic, yet how these dynamics are regulated and the role they play in genome function is poorly understood. Here, we utilized acute depletion of NIPBL to characterize the role of cohesin-mediated loop extrusion in vivo. Using this approach, we found that many chromatin loops are rapidly diminished upon loss of NIBPL, consistent with recent single locus imaging studies showing that chromatin loops are transient. However, we also identified cohesin-dependent chromatin loops that are associated with distinct chromatin states and may be "long-lived", given that they require NIPBL for their establishment upon mitotic exit, but are persistent when NIPBL is depleted from interphase cells. In addition to the reformation of 3D genome structures, mitotic exit coincides with widespread transcriptional activation. We found that NIPBL is essential for establishing the expression of lineage-defining genes during the M-G1 transition but has diminished impact on the steady-state maintenance of their expression. At genes sensitive to its depletion, NIPBL supports a unique local genome organization defined by greater spatial proximity to nearby super-enhancers and weaker transcription start site insulation of genomic contacts. Overall, we show that NIPBL-mediated loop extrusion is critical to genome organization and transcription regulation in vivo.

molecular biology↗