Background and design of the Physical Frailty and Symptom Monitoring and Management Behaviors in Heart Failure (PRISM-HF) study: A mixed methods study.

Background: Many adults with heart failure (HF) are physically frail and have worse outcomes. While the biological profile of physical frailty in HF has been examined, the behavioral profile remains unstudied. Physical frailty may impact self-care behaviors, particularly symptom monitoring and management (SMM), which in turn results in adverse outcomes.

Notch signaling and Bsh homeodomain activity are integrated to diversify lamina neuron types.

Notch signaling is an evolutionarily conserved pathway for specifying binary neuronal fates, yet how it specifies different fates in different contexts remains elusive. In our accompanying paper, using the lamina neuron types (L1-L5) as a model, we show that the primary homeodomain transcription factor (HDTF) Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates. Here we test the hypothesis that Notch signaling enables Bsh to differentially specify L4 and L5 fates.

Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity.

How our brain generates diverse neuron types that assemble into precise neural circuits remains unclear. Using lamina neuron types (L1-L5), we show that the primary homeodomain transcription factor (HDTF) brain-specific homeobox (Bsh) is initiated in progenitors and maintained in L4/L5 neurons to adulthood. Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates while repressing the HDTF Zfh1 to prevent ectopic L1/L3 fates (control: L1-L5; Bsh-knockdown: L1-L3), thereby generating lamina neuronal diversity for normal visual sensitivity.